Frailty as a predictor of mortality in older adults within 5 years of psychiatric admission

Objectives Older adults with psychiatric disorders have a substantially lower life expectancy than age-matched controls. Knowledge of risk factors may lead to targeting treatment and interventions to reduce this gap in life expectancy. In this study, we investigated whether frailty independently predicts mortality in older patients following an acute admission to a geriatric psychiatry hospital. Methods Clinical cohort study with a 5-year follow-up of 120 older patients admitted to a psychiatric hospital between February 2009 and September 2010. On admission, we assessed frailty with a frailty index (FI). We applied Cox regression analyses with time to death as the dependent variable, to examine whether the FI was a predictor for mortality, adjusted for age, sex, level of education, multimorbidity (Cumulative Illness Rating Scale for Geriatrics, CIRS-G scores), functional status (Barthel Index), neuropsychiatric symptoms (NPS), and severity of psychiatric symptoms at admission (Clinical Global Impressions Scale of Severity). Results Of the 120 patients, 63 (53%) patients were frail (FI >= 0.25), and 59 (49%) had died within 5 years. The FI predicted mortality with a hazard ratio (HR) of 1.78 (95% CI, 1.06-2.98) per 0.1 point increase, independent of the covariates. Co-morbidity measured by the CIRS-G and functional status measured by the Barthel Index were not significantly associated. Conclusions Frailty was a strong predictor of mortality, independent of age, gender, multimorbidity, and functional status. This implies that frailty may be helpful in targeting inpatient psychiatric treatment and aftercare according to patients' life expectancy

Myocardin-Related Transcription Factors A and B Are Key Regulators of TGF-β1-Induced Fibroblast to Myofibroblast Differentiation

Myofibroblasts are contractile, smooth muscle-like cells that are characterized by the de novo expression of smooth muscle α-actin (SMαA) and normally function to assist in wound closure, but have been implicated in pathological contractures. Transforming growth factor β-1 (TGF-β1) helps facilitate the differentiation of fibroblasts into myofibroblasts, but the exact mechanism by which this differentiation occurs, in response to TGF-β1, remains unclear. Myocardin-related transcription factors A and B (MRTFs, MRTF-A/B) are transcriptional co-activators that regulate the expression of smooth muscle-specific cytoskeletal proteins, including SMαA, in smooth muscle cells and fibroblasts. In this study, we demonstrate that TGF-β1 mediates myofibroblast differentiation and the expression of a contractile gene program through the actions of the MRTFs. Transient transfection of a constitutively active MRTF-A induced an increase in the expression of SMαA and other smooth muscle-specific cytoskeletal proteins, and an increase in myofibroblast contractility, even in the absence of TGF-β1. MRTF-A/B knockdown, in TGF-β1-differentiated myofibroblasts, resulted in decreased smooth muscle-specific cytoskeletal protein expression levels and reduced contractile force generation, as well as a decrease in focal adhesion size and number. These results provide direct evidence that the MRTFs are mediators of myofibroblast differentiation in response to TGF-β1

Quantifying resilience of humans and other animals

All life requires the capacity to recover from challenges that are as inevitable as they are unpredictable. Understanding this resilience is essential for managing the health of humans and their livestock. It has long been difficult to quantify resilience directly, forcing practitioners to rely on indirect static indicators of health. However, measurements from wearable electronics and other sources now allow us to analyze the dynamics of physiology and behavior with unsurpassed resolution. The resulting flood of data coincides with the emergence of novel analytical tools for estimating resilience from the pattern of micro-recoveries observed in natural time series. Such dynamic indicators of resilience (DIORs) may be used to monitor the risk of systemic failure across systems ranging from organs to entire organisms. These tools invite a fundamental rethink of our approach to the adaptive management of health and resilience

Mammary stem cells have myoepithelial cell properties.

Contractile myoepithelial cells dominate the basal layer of the mammary epithelium and are considered to be differentiated cells. However, we observe that up to 54% of single basal cells can form colonies when seeded into adherent culture in the presence of agents that disrupt actin-myosin interactions, and on average, 65% of the single-cell-derived basal colonies can repopulate a mammary gland when transplanted in vivo. This indicates that a high proportion of basal myoepithelial cells can give rise to a mammary repopulating unit (MRU). We demonstrate that myoepithelial cells, flow-sorted using two independent myoepithelial-specific reporter strategies, have MRU capacity. Using an inducible lineage-tracing approach we follow the progeny of myoepithelial cells that express α-smooth muscle actin and show that they function as long-lived lineage-restricted stem cells in the virgin state and during pregnancy.This work was funded by Cancer Research UK, Breast Cancer Campaign, the University of Cambridge, Hutchison Whampoa Limited, La Ligue Nationale Contre le Cancer (Equipe Labelisée 2013) and a grant from Agence Nationale de la Recherche ANR- 08-BLAN-0078-01 to M.A.G.This is the author accepted manuscript. The final version is available from Nature at http://www.nature.com/ncb/journal/vaop/ncurrent/full/ncb3025.html

How to Conduct International Geriatric Rehabilitation Research?

With an ageing global population and an increasing focus on aging in place, the number of people in need of geriatric rehabilitation (GR) is rapidly increasing. As current GR practice is very heterogenous, cross-country comparisons could allow us to learn from each other and optimise the effectiveness of GR. However, international GR research comes with many challenges. This article summarises the facilitators and barriers relating to the recruitment of rehabilitation centres, the inclusion of patients, and data collection, as experienced by experts in the field of international GR research. The three most important methodological recommendations for conducting cross-national collaborative research in the field of GR are (1) make use of existing (inter)national networks and social media to aid recruitment of GR centres; (2) clearly define the GR treatment, setting, and patient characteristics in the inclusion criteria; and (3) use a hierarchical study structure to communicate transparently and regularly with both national and local coordinators. International GR research would greatly benefit from the implementation of a core dataset in regular GR care. Therefore, future studies should focus on developing an international consensus regarding the outcomes and corresponding cross-culturally validated measurement instruments to be used during GR

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.Geriatrics in primary carePublic Health and primary car

A lower global lung ultrasound score is associated with higher likelihood of successful extubation in invasively ventilated COVID-19 patients

Lung ultrasound (LUS) can be used to assess loss of aeration, which is associated with outcome in patients with coronavirus disease 2019 (COVID-19) presenting to the emergency department. We hypothesized that LUS scores are associated with outcome in critically ill COVID-19 patients receiving invasive ventilation. This retrospective international multicenter study evaluated patients with COVID-19-related acute respiratory distress syndrome (ARDS) with at least one LUS study within 5 days after invasive mechanical ventilation initiation. The global LUS score was calculated by summing the 12 regional scores (range 0-36). Pleural line abnormalities and subpleural consolidations were also scored. The outcomes were successful liberation from the ventilator and intensive care mortality within 28 days, analyzed with multistate, competing risk proportional hazard models. One hundred thirty-seven patients with COVID-19-related ARDS were included in our study. The global LUS score was associated with successful liberation from mechanical ventilation (hazard ratio [HR]: 0.91 95% confidence interval [CI] 0.87-0.96; P = 0.0007) independently of the ARDS severity, but not with 28 days mortality (HR: 1.03; 95% CI 0.97-1.08; P = 0.36). Subpleural consolidation and pleural line abnormalities did not add to the prognostic value of the global LUS score. Examinations within 24 hours of intubation showed no prognostic value. To conclude, a lower global LUS score 24 hours after invasive ventilation initiation is associated with increased probability of liberation from the mechanical ventilator COVID-19 ARDS patients, independently of the ARDS severity.Pathogenesis and treatment of chronic pulmonary disease

Fact or Factitious? A Psychobiological Study of Authentic and Simulated Dissociative Identity States

BACKGROUND: Dissociative identity disorder (DID) is a disputed psychiatric disorder. Research findings and clinical observations suggest that DID involves an authentic mental disorder related to factors such as traumatization and disrupted attachment. A competing view indicates that DID is due to fantasy proneness, suggestibility, suggestion, and role-playing. Here we examine whether dissociative identity state-dependent psychobiological features in DID can be induced in high or low fantasy prone individuals by instructed and motivated role-playing, and suggestion. METHODOLOGY/PRINCIPAL FINDINGS: DID patients, high fantasy prone and low fantasy prone controls were studied in two different types of identity states (neutral and trauma-related) in an autobiographical memory script-driven (neutral or trauma-related) imagery paradigm. The controls were instructed to enact the two DID identity states. Twenty-nine subjects participated in the study: 11 patients with DID, 10 high fantasy prone DID simulating controls, and 8 low fantasy prone DID simulating controls. Autonomic and subjective reactions were obtained. Differences in psychophysiological and neural activation patterns were found between the DID patients and both high and low fantasy prone controls. That is, the identity states in DID were not convincingly enacted by DID simulating controls. Thus, important differences regarding regional cerebral bloodflow and psychophysiological responses for different types of identity states in patients with DID were upheld after controlling for DID simulation. CONCLUSIONS/SIGNIFICANCE: The findings are at odds with the idea that differences among different types of dissociative identity states in DID can be explained by high fantasy proneness, motivated role-enactment, and suggestion. They indicate that DID does not have a sociocultural (e.g., iatrogenic) origin