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Abstract Background The catastrophic health expenditure of older adults results in serious consequences; however, the issue of whether cognitive status and living situations contribute to such financial burdens is uncertain. Our aim was to compare the differences in catastrophic health expenditure between adults living alone with cognitive impairment and those adults living with others and with normal cognition. Methods We identified 909 observations of participants living alone with cognitive impairment (cases) and 37,432 observations of participants living with others and with normal cognition (comparators) from the 2011/2012, 2013, 2015 and 2018 waves of the China Health and Retirement Longitudinal Study (CHARLS). We used propensity score matching (1:2) to create matched cases and comparators in a covariate-adjusted logistic regression analysis. Catastrophic health expenditure was defined as an out-of-pocket cost for health care ≥40% of a household’s capacity to pay. Results In comparison with participants living with others and with normal cognition, those adults living alone with cognitive impairment reported a higher percentage of catastrophic health expenditure (19.5% vs. 11.8%, respectively, P

Abstract Background Physical activity may be both a risk and protective factor for falls and fall-related fractures. Despite its positive effects on muscle and bone health, physical activity also increases exposure to situations where falls and fractures occur. This paradox could possibly be explained by frailty status. Therefore, the aim of this study was to investigate the associations between physical activity and both falls and fractures, and to determine whether frailty modifies the association of physical activity with falls, and fractures. Methods Data of 311 community-dwelling participants aged 75 years or older from the Longitudinal Aging Study Amsterdam, who participated in a three-year longitudinal study with five nine-monthly measurements between 2015/2016 and 2018/2019. Their mean age was 81.1 (SD 4.8) years and frailty was present in 30.9% of the participants. Physical activity in minutes per day was objectively assessed with an inertial sensor (Actigraph) for seven consecutive days. Falls and fractures were assessed every nine months using self-report during an interview over a follow-up period of three years. Frailty was determined at baseline using the frailty index. Associations were estimated using longitudinal logistic regression analyses based on generalized estimating equations. Results No association between physical activity and falls was found (OR = 1.00, 95% CI: 0.99–1.00). Fall risk was higher in frail compared to non-frail adults (OR = 2.21, 95% CI: 1.33–3.68), but no effect modification was seen of frailty on the association between physical activity and falls. Also no relation between physical activity and fractures was found (OR = 1.00, 95% CI: 0.99–1.01). Fracture risk was higher in frail compared to non-frail adults (OR = 2.81, 95% CI: 1.02–7.75), but also no effect modification of frailty was present in the association between physical activity and fractures. Conclusions No association between physical activity and neither falls nor fractures was found, and frailty appeared not to be an effect modifier. However, frailty was a risk factor for falls and fractures in this population of older adults. Our findings suggest that physical activity can be safely recommended in non-frail and frail populations for general health benefits, without increasing the risk of falls.

Abstract Objective Callous-unemotional (CU) traits are associated with a more severe and chronic trajectory of antisocial behavior. The present study aimed to identify different classes of CU and anxiety and to compare these classes on overt and covert antisocial behavior and several clinical correlates. Method In a prospective high-risk cohort of adolescents (N = 679; mean age = 14.77, SD = 0.81), latent profile analysis was conducted using CU traits and anxiety symptoms as indicators, and multi-informant aggressive and rule breaking behavior as distal outcomes. Post-hoc analyses with binary logistic regression and a series of ANCOVA were performed on identified classes assessing violent aggression, property offending, and clinical correlates. Results Three classes were found, a reference group (low CU, low anxiety; N = 500), a high CU-low anxiety group (N = 98), and an intermediate CU-high anxious group (N = 81). The high CU-low anxiety group scored highest on property offenses, while the intermediate CU-high anxious group scored highest on aggressive behavior. The intermediate CU-high anxious group scored highest on psychotic experiences, while the high CU group scored highest on internet gaming addiction problems and bullying victimization. Conclusion These findings provide further evidence for diverse variants of CU traits in a high-risk community sample. Future prospective studies should point out whether and to what extent adolescents with CU traits with and without anxiety develop criminal careers and psychiatric disorders in adulthood.

Introduction In ageing societies, the number of older adults with complex chronic conditions (CCCs) is rapidly increasing. Care for older persons with CCCs is challenging, due to interactions between multiple conditions and their treatments. In home care and nursing homes, where most older persons with CCCs receive care, professionals often lack appropriate decision support suitable and sufficient to address the medical and functional complexity of persons with CCCs. This EU-funded project aims to develop decision support systems using high-quality, internationally standardised, routine care data to support better prognostication of health trajectories and treatment impact among older persons with CCCs.Methods and analysis Real-world data from older persons aged ≥60 years in home care and nursing homes, based on routinely performed comprehensive geriatric assessments using interRAI systems collected in the past 20 years, will be linked with administrative repositories on mortality and care use. These include potentially up to 51 million care recipients from eight countries: Italy, the Netherlands, Finland, Belgium, Canada, USA, Hong Kong and New Zealand. Prognostic algorithms will be developed and validated to better predict various health outcomes. In addition, the modifying impact of pharmacological and non-pharmacological interventions will be examined. A variety of analytical methods will be used, including techniques from the field of artificial intelligence such as machine learning. Based on the results, decision support tools will be developed and pilot tested among health professionals working in home care and nursing homes.Ethics and dissemination The study was approved by authorised medical ethical committees in each of the participating countries, and will comply with both local and EU legislation. Study findings will be shared with relevant stakeholders, including publications in peer-reviewed journals and presentations at national and international meetings.

In 2008 ging in Nederland het Nationaal Programma Ouderenzorg (NPO) van start. Met een budget van meer dan 80 miljoen euro zijn tot 2016 ruim 200 onderzoeks- en implementatieprojecten uitgevoerd met als doel om de zorg voor kwetsbare ouderen te verbeteren. Het ging daarbij om een brede definitie van zorg, waaronder medische zorg, welzijn, langdurige zorg en mantelzorg. Het NPO werd gekenmerkt door een grote diversiteit aan projecten, verspreid over het hele land, waarbij de universitair medische centra (UMC’s) een coördinerende rol hadden. Dit resulteerde in een enorme boost voor het onderzoek rond het thema kwetsbaarheid, wat ook internationaal goed zichtbaar was: er verschenen tijdens het NPO diverse toonaangevende wetenschappelijke publicaties van Nederlandse onderzoekers.1 2 3 4 Deze publicaties liepen uiteen van prevalentiecijfers van kwetsbaarheid4 tot aan gegevens over de effectiviteit van interventies voor thuiswonende kwetsbare ouderen1. Nu, 15 jaar later, is het een goed moment om eens te bekijken hoeveel aandacht er nog is voor onderzoek naar kwetsbaarheid bij ouderen in Nederland. Wat is de huidige infrastructuur van kwetsbaarheidsonderzoek en welke kansen liggen er voor toekomstig onderzoek?

BackgroundCompared with adults with normal glucose metabolism, those with prediabetes tend to be frail. However, it remains poorly understood whether frailty could identify adults who are most at risk of adverse outcomes related to prediabetes. ObjectiveWe aimed to systematically evaluate the associations between frailty, a simple health indicator, and risks of multiple adverse outcomes including incident type 2 diabetes mellitus (T2DM), diabetes-related microvascular disease, cardiovascular disease (CVD), chronic kidney disease (CKD), eye disease, dementia, depression, and all-cause mortality in late life among middle-aged adults with prediabetes. MethodsWe evaluated 38,950 adults aged 40 years to 64 years with prediabetes using the baseline survey from the UK Biobank. Frailty was assessed using the frailty phenotype (FP; range 0-5), and participants were grouped into nonfrail (FP=0), prefrail (1≤FP≤2), and frail (FP≥3). Multiple adverse outcomes (ie, T2DM, diabetes-related microvascular disease, CVD, CKD, eye disease, dementia, depression, and all-cause mortality) were ascertained during a median follow-up of 12 years. Cox proportional hazards regression models were used to estimate the associations. Several sensitivity analyses were performed to test the robustness of the results. ResultsAt baseline, 49.1% (19,122/38,950) and 5.9% (2289/38,950) of adults with prediabetes were identified as prefrail and frail, respectively. Both prefrailty and frailty were associated with higher risks of multiple adverse outcomes in adults with prediabetes (P for trend

Background: Alterations in stress regulation and function of the hypothalamic-pituitary-adrenal (HPA) axis during infancy may be a risk factor for the development of psychopathology later in life. Maternal childhood trauma, depression, anxiety and stressful life events are individually associated with HPA axis dysregulation. Less is known about their interdependent influence on maternal and infant stress regulation in at risk populations. In a sample of mothers with a history of depressive-, and/or anxiety disorders and their infants we explored if a history of maternal childhood trauma, current depressive and anxiety symptomatology, and recent life events were associated with maternal and infant long-term cortisol levels three months postpartum. Methods: Data were available of 89 mothers and 49 infants. All mothers fulfilled criteria for a lifetime depressive or anxiety disorder. Diagnosis was established with a diagnostic interview. Current depressive symptomatology was assessed with the Edinburgh Postnatal Depression Scale (EPDS), current anxiety with the State-Trait Anxiety Inventory (STAI), maternal childhood trauma with the Childhood Trauma Questionnaire (CTQ) and recent life events with the Everyday Problem Checklist (EPC). Maternal and infant hair cortisol concentrations (HCC) were quantified with liquid chromatography with tandem mass spectrometry (LC-MS/MS) three months after birth. Total scores of the CTQ and subscales, EPDS, STAI, and EPC were regressed on maternal and infant HCC using regression analyses. Differences in HCC regarding trauma history were tested with t-tests. Potential confounders were identified and adjusted for. Results: In regression analyses, a positive curvilinear relationship was found between CTQ total score and maternal HCC (n = 83, B = 0.076, SE 0.033, p = .021), but not for current depression (n = 88, B = −0.001, SE 0.011, p = .931), current anxiety (n = 88, B = 0.002, SE 0.004, p = .650) or recent life events (n = 89, B = 0.018, SE 0.032, p = .568). Analyses were adjusted for confounders. A negative linear relationship was found between maternal CTQ score and infant HCC (n = 49, β = −0.264, B = −0.006, SE 0.003, p = .052), but not for current maternal depression (n = 45, β = −0.182, B = −0.011, SE 0.008, p = .164), current maternal anxiety (n = 45, β = −0.209, B = −0.005, SE 0.003, p = .113) or recent life events (n = 46, β = −0.128, B = −0.022, SE 0.023, p = .325). Analyses were adjusted for relevant infant hair characteristics. Specifically, maternal emotional and physical neglect were related to HCC in both mothers and infants. Conclusions: Results suggest that maternal childhood trauma is more prominent in altering maternal and infant long-term cortisol levels than perinatal depressive and anxiety symptomatology or recent life stressors in mothers with a history of depressive and/or anxiety disorders, and their infants. As infants of mothers with psychopathology are at increased risk for later psychiatric disease, future studies should investigate the interplay of possible risk factors for transgenerational transmission, intra-uterine programming of the HPA axis, including (epi-)genetic phenomena, of the HPA axis, and the influence of parenting impairment.

Abstract Background Aging metrics incorporating cognitive and physical function are not fully understood, hampering their utility in research and clinical practice. This study aimed to determine the proportions of vulnerable persons identified by three existing aging metrics that incorporate cognitive and physical function and the associations of the three metrics with mortality. Methods We considered three existing aging metrics including the combined presence of cognitive impairment and physical frailty (CI-PF), the frailty index (FI), and the motoric cognitive risk syndrome (MCR). We operationalized them using data from the China Health and Retirement Longitudinal Study (CHARLS) and the US National Health and Nutrition Examination Survey (NHANES). Logistic regression models or Cox proportional hazards regression models, and receiver operating characteristic curves were used to examine the associations of the three metrics with mortality. Results In CHARLS, the proportions of vulnerable persons identified by CI-PF, FI, and MCR were 2.2, 16.6, and 19.6%, respectively. Each metric predicted mortality after adjustment for age and sex, with some variations in the strength of the associations (CI-PF, odds ratio (OR) (95% confidence interval (CI)) 2.87 (1.74–4.74); FI, OR (95% CI) 1.94 (1.50–2.50); MCR, OR (95% CI) 1.27 (1.00–1.62)). CI-PF and FI had additional predictive utility beyond age and sex, as demonstrated by integrated discrimination improvement and continuous net reclassification improvement (all P

Increasing evidence exists that the gut microbiome influences toxicity as well as outcomes in a variety of cancers. To investigate the role of the gut microbiome in pediatric neuro-oncology, microbiome analysis has been included in multiple prospective pediatric neuro-oncology clinical trials (NCT05009992, NCT04732065, NCT04775485). In these trials, the OMNIgene-GUTtm preservation tubes are used for the collection of the feces. OMNIgene-GUTtm has demonstrated reliability in preserving the composition of the gut microbiome in adults; however, its validation for use in the pediatric population remains limited. Therefore, we compared the quality of the DNA by 16S rRNA gene sequencing after various methods of stabilizing fecal samples in pediatric populations, from the direct freeze method at − 80 °C to preserving samples with OMNIgene-GUTtm at room temperature for various durations. Our results showed that there were no statistically significant differences between the alpha-diversity, and beta-diversity. However, pairwise differential abundance analyses demonstrated that OMNIgene-GUT™ is superior in maintaining microbial community structure compared to storing samples without any preservation method. With the OMNIgene-GUTtm's stabilization of the fecal samples being superior and its ease-of-use benefits, it proves to be a valid and ideal method of stabilizing fecal samples for current and future pediatric clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: Neutrophils play a dichotomous role in community-acquired pneumonia (CAP), providing protection and potentially causing damage. Existing research on neutrophil function in CAP relies on animal studies, leaving a gap in patient-centered investigations. Methods: We used mass spectrometry to characterize the neutrophil proteome of moderately ill CAP patients at general ward admission and related the proteome to controls and clinical outcomes. Results: We prospectively included 57 CAP patients and 26 controls and quantified 3482 proteins in neutrophil lysates and 386 proteins in concurrently collected plasma. The extensively studied granule-related proteins in animal models did not drive the neutrophil proteome changes associated with human CAP. Proteome alterations were primarily characterized by an increased abundance of proteins related to (aerobic) metabolic activity and (m)RNA translation/processing, concurrent with a diminished presence of cytoskeletal organization-related proteins (all pathways p<0.001). Higher and lower abundances of specific proteins, primarily constituents of these pathways, were associated with prolonged time to clinical stability in CAP. Moreover, we identified a pronounced presence of platelet-related proteins in neutrophil lysates of particularly viral CAP patients, suggesting the existence of neutrophil-platelet complexes in non-critically ill CAP patients. Of the proteins measured in neutrophils, 4.3% were detected in plasma. Discussion: Our study presents new perspectives on the neutrophil proteome associated with CAP, laying the groundwork for forthcoming patient-centred investigations. Our results could pave the way for targeted strategies to fine-tune neutrophil responses, potentially improving CAP outcomes. [ABSTRACT FROM AUTHOR]

Background It is unclear whether social isolation and loneliness may precede frailty status or whether frailty may precipitate social isolation and loneliness. We investigated the reciprocal and temporal sequence of social isolation, loneliness, and frailty among older adults across 21 years. Methods We used seven waves of the Longitudinal Aging Study Amsterdam from 2302 Dutch older adults (M = 72.6 years, SD = 8.6, 52.1% female) ages 55 or older. Using random intercept cross-lagged panel models, we investigated between- and within-person associations of social isolation and loneliness with frailty. Frailty was measured using the Frailty Index. Loneliness was measured using the 11-item De Jong Gierveld Loneliness Scale. Social isolation was measured using a multi-domain 6-item scale. Results Social isolation and loneliness were weakly correlated across waves. At the between-person level, individuals with higher levels of frailty tended to have higher levels of social isolation but not loneliness. At the within-person level, the cross-lagged paths indicated that earlier frailty status predicted future social isolation and loneliness over time. However, prior social isolation was not associated with subsequent frailty except at time point 5 (T5). Loneliness at specific time points (T1, T4 and T6) predicted greater frailty at later time points (T2, T5 and T7). The results also supported reciprocal and contemporaneous relations between social isolation, loneliness and frailty. Conclusions Social isolation and loneliness are potential outcomes of frailty. Public health policies and health practitioners should prioritise interventions targeting social connection among older adults with pre-frailty or frailty. [ABSTRACT FROM AUTHOR]

The teacher-student relationship plays an important role in the academic and behavioral development of primary school children with externalizing problem behavior. However, such problem behavior often threatens the quality of the teacher-student relationship. Teacher-focused coaching intervention Key2Teach aims to improve elements of the relationship between teachers and students with externalizing problem behavior and consists of two phases and four building blocks. This intervention provides primary school teachers with insight into their mental representation of the relationship and opportunities to practice functional interaction skills. In a randomized controlled trial (RCT), effects of Key2Teach on different aspects of the relationship between teachers and students with externalizing problem behavior were examined. In two cohorts, 103 dyads consisting of a teacher and a student with externalizing problem behavior in grades 3-6 were assessed three times during a school year. Fifty-three dyads received the intervention (intervention group), whereas 50 dyads received no intervention (control group). Data were collected on teacher-reported teacher-student closeness and conflict, and on teacher interaction skills in various domains. Results show a significant increase in closeness and a decrease in conflict as a result of Key2Teach, with substantial effect sizes. No effects on teacher interaction skills were found. This study indicates that Key2Teach may help teachers to improve elements of the relationship they have with students with externalizing problem behavior. Implications for practice and future research are discussed.

Teaching students with externalising problem behaviours is difficult for teachers, as it challenges the relationship that teachers engage in with their students. In this study, effects of Key2Teach on externalising and social-emotional problem behaviours and the mediating role of conflict in the teacher-student relationship were studied using a randomised controlled trial (RCT)-design. In two cohorts, 103 teacher-student dyads and peer-students (n = 1643) were assessed two times during a school year. Fifty-three dyads received the intervention (experimental group), whereas 50 dyads received no intervention (control group). Data were collected on teacher-reported externalising and social-emotional problem behaviours in students, and on teacher-student conflict. For dyad-students, results showed a direct effect of Key2Teach on conduct problems and an indirect effect, via teacher-student conflict, for hyperactivity problems. No effects on social-emotional problems were established. For peer-students, results showed indirect effects on externalising problems and direct effects on social-emotional problems. Implications for practice and future research are discussed.

Abstract Background The ability to accurately predict survival in older adults is crucial as it guides clinical decision making. The added value of using various health indicators as well as changes in these indicators for predicting mortality remains unclear. The aim of this study was to investigate whether changes in health indicators such as frailty and physical performance improve mortality predictions in old age. Methods This is a population based prospective cohort study on 995 community-dwelling people aged 68–92 years from the Longitudinal Aging Study Amsterdam. Two measurements at a three-year interval (1995/1996 and 1998/1999) were available for the frailty index, frailty phenotype, grip strength, walking speed, and Mini-Mental State Examination (MMSE). Cox regression was used to analyze mortality risks associated with the current health status and changes in health, with mortality data up to 2017. The extent to which these health indicators improved mortality predictions compared to models with age and sex only was assessed by the area under the receiver operating characteristic curve (AUC). Results The AUC of age and sex for five-year mortality was 72.8% (95% CI 69.0 – 76.5) and was the lowest in the oldest old (age > 80.5 years). The added AUC of the current status of health indicators ranged from 0.7 to 3.3%. The added AUC of the three-year change was lower, ranging from -0.0 to 1.1%, whereas the added AUC of three-year change and current status combined was similar to current status alone, ranging from 0.6 to 3.2%. Across age, the added AUC of current status was highest in the oldest old, however there was no such pattern using three-year change. Overall, the frailty index appeared to improve mortality predictions the most, followed by the frailty phenotype, MMSE, grip strength, and walking speed. Conclusions Current health status improved mortality predictions better than changes in health. Its contribution was highest in the oldest old, but the added value to models with age and sex only was limited.

Objectives The aim of this study was to develop an index to measure older adults’ exposure to the COVID-19 pandemic and to study its association with various domains of functioning.Design Cross-sectional study.Setting The Longitudinal Aging Study Amsterdam (LASA), a cohort study in the Netherlands.Participants Community-dwelling older adults aged 62–102 years (n=1089) who participated in the LASA COVID-19 study (June–September 2020), just after the first wave of the pandemic.Primary outcome measures A 35-item COVID-19 exposure index with a score ranging between 0 and 1 was developed, including items that assess the extent to which the COVID-19 situation affected daily lives of older adults. Descriptive characteristics of the index were studied, stratified by several sociodemographic factors. Logistic regression analyses were performed to study associations between the exposure index and several indicators of functioning (functional limitations, anxiety, depression and loneliness).Results The mean COVID-19 exposure index score was 0.20 (SD 0.10). Scores were relatively high among women and in the southern region of the Netherlands. In models adjusted for sociodemographic factors and prepandemic functioning (2018–2019), those with scores in the highest tertile of the exposure index were more likely to report functional limitations (OR: 2.24; 95% CI: 1.48 to 3.38), anxiety symptoms (OR: 3.14; 95% CI: 1.82 to 5.44), depressive symptoms (OR: 2.49; 95% CI: 1.55 to 4.00) and loneliness (OR: 2.97; 95% CI: 2.08 to 4.26) than those in the lowest tertile.Conclusions Among older adults in the Netherlands, higher exposure to the COVID-19 pandemic was associated with worse functioning in the physical, mental and social domain. The newly developed exposure index may be used to identify persons for whom targeted interventions are needed to maintain or improve functioning during the pandemic or postpandemic.

Aims: Robotic magnetic navigation (RMN) provides increased catheter precision and stability. Formerly, only the CARTO 3 mapping system was integrated with the RMN system (CARTO-RMN). Recently, a novel high-resolution non-contact mapping system (AcQMap) has been integrated with the RMN system (AcQMap-RMN) for the treatment of atrial fibrillation (AF) and atrial tachycardias (AT). We aim to compare the safety, efficiency, and efficacy of AcQMap-RMN with CARTO-RMN guided catheter ablation (CA) procedures. Material and methods: In this prospective registry, procedural safety efficiency and outcome data from total of 238 consecutive patients (147 AcQMap-RMN and 91 CARTO-RMN patients) were compared. Results: AcQMap-RMN is non-inferior in the primary endpoint of safety as compared to CARTO-RMN across the whole group (overall procedural complications in 5 (3.4%) vs. 3 (3.3%) patients, p = 1.0). Overall procedure durations were longer and associated with more fluoroscopy use with AcQMap-RMN (172.5 vs. 129.6 min, p