An exploration of social and economic outcome and associated health-related quality of life after critical illness in general intensive care unit survivors: a 12-month follow-up study.

INTRODUCTION: The socio-economic impact of critical illnesses on patients and their families in Europe has yet to be determined. The aim of this exploratory study was to estimate changes in family circumstances, social and economic stability, care requirements and access to health services for patients during their first 12 months after ICU discharge. METHODS: Multi-center questionnaire-based study of survivors of critical illness at 6 and 12 months after ICU discharge. RESULTS: Data for 293 consenting patients who spent greater than 48 hours in one of 22 UK ICUs were obtained at 6 and 12 months post-ICU discharge. There was little evidence of a change in accommodation or relationship status between pre-admission and 12 months following discharge from an ICU. A negative impact on family income was reported by 33% of all patients at 6 months and 28% at 12 months. There was nearly a 50% reduction in the number of patients who reported employment as their sole source of income at 12 months (19% to 11%) compared with pre-admission. One quarter of patients reported themselves in need of care assistance at 6 months and 22% at 12 months. The majority of care was provided by family members (80% and 78%, respectively), for half of whom there was a negative impact on employment. Amongst all patients receiving care, 26% reported requiring greater than 50 hours a week. Following discharge, 79% of patients reported attending their primary care physician and 44% had seen a community nurse. Mobility problems nearly doubled between pre-admission and 6 months (32% to 64%). Furthermore, 73% reported moderate or severe pain at 12 months and 44% remained significantly anxious or depressed. CONCLUSIONS: Survivors of critical illness in the UK face a negative impact on employment and commonly have a care requirement after discharge from hospital. This has a corresponding negative impact on family income. The majority of the care required is provided by family members. This effect was apparent by 6 months and had not materially improved by 12 months. This exploratory study has identified the potential for a significant socio-economic burden following critical illness

Investor heterogeneity and the cross-section of U.K. investment trust performance

We use the upper and lower bounds derived by Ferson and Lin (2010) to examine the impact of investor heterogeneity on the performance of U.K. investment trusts relative to alternative linear factor models. We find using the upper bounds that investor heterogeneity has an important impact for nearly all investment trusts. The upper bounds are large in economic terms and significantly different from zero. We find no evidence of any trusts where all investors agree on the sign of performance beyond what we expect by chance. Using the lower bound, we find that trusts with a larger disagreement about trust performance have a weaker relation between the trust premium and past Net Asset Value (NAV) performance

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

A survey of integral α-helical membrane proteins

Membrane proteins serve as cellular gatekeepers, regulators, and sensors. Prior studies have explored the functional breadth and evolution of proteins and families of particular interest, such as the diversity of transport-associated membrane protein families in prokaryotes and eukaryotes, the composition of integral membrane proteins, and family classification of all human G-protein coupled receptors. However, a comprehensive analysis of the content and evolutionary associations between membrane proteins and families in a diverse set of genomes is lacking. Here, a membrane protein annotation pipeline was developed to define the integral membrane genome and associations between 21,379 proteins from 34 genomes; most, but not all of these proteins belong to 598 defined families. The pipeline was used to provide target input for a structural genomics project that successfully cloned, expressed, and purified 61 of our first 96 selected targets in yeast. Furthermore, the methodology was applied (1) to explore the evolutionary history of the substrate-binding transmembrane domains of the human ABC transporter superfamily, (2) to identify the multidrug resistance-associated membrane proteins in whole genomes, and (3) to identify putative new membrane protein families

Differences in Muscle Protein Synthesis and Anabolic Signaling in the Postabsorptive State and in Response to Food in 65–80 Year Old Men and Women

Women have less muscle than men but lose it more slowly during aging. To discover potential underlying mechanism(s) for this we evaluated the muscle protein synthesis process in postabsorptive conditions and during feeding in twenty-nine 65–80 year old men (n = 13) and women (n = 16). We discovered that the basal concentration of phosphorylated eEF2Thr56 was ∼40% less (P<0.05) and the basal rate of MPS was ∼30% greater (P = 0.02) in women than in men; the basal concentrations of muscle phosphorylated AktThr308, p70s6kThr389, eIF4ESer209, and eIF4E-BP1Thr37/46 were not different between the sexes. Feeding increased (P<0.05) AktThr308 and p70s6kThr389 phosphorylation to the same extent in men and women but increased (P<0.05) the phosphorylation of eIF4ESer209 and eIF4E-BP1Thr37/46 in men only. Accordingly, feeding increased MPS in men (P<0.01) but not in women. The postabsorptive muscle mRNA concentrations for myoD and myostatin were not different between sexes; feeding doubled myoD mRNA (P<0.05) and halved that of myostatin (P<0.05) in both sexes. Thus, there is sexual dimorphism in MPS and its control in older adults; a greater basal rate of MPS, operating over most of the day may partially explain the slower loss of muscle in older women

Differences in Muscle Protein Synthesis and Anabolic Signaling in the Postabsorptive State and in Response to Food in 65–80 Year Old Men and Women

Women have less muscle than men but lose it more slowly during aging. To discover potential underlying mechanism(s) for this we evaluated the muscle protein synthesis process in postabsorptive conditions and during feeding in twenty-nine 65–80 year old men (n = 13) and women (n = 16). We discovered that the basal concentration of phosphorylated eEF2Thr56 was ∼40% less (P<0.05) and the basal rate of MPS was ∼30% greater (P = 0.02) in women than in men; the basal concentrations of muscle phosphorylated AktThr308, p70s6kThr389, eIF4ESer209, and eIF4E-BP1Thr37/46 were not different between the sexes. Feeding increased (P<0.05) AktThr308 and p70s6kThr389 phosphorylation to the same extent in men and women but increased (P<0.05) the phosphorylation of eIF4ESer209 and eIF4E-BP1Thr37/46 in men only. Accordingly, feeding increased MPS in men (P<0.01) but not in women. The postabsorptive muscle mRNA concentrations for myoD and myostatin were not different between sexes; feeding doubled myoD mRNA (P<0.05) and halved that of myostatin (P<0.05) in both sexes. Thus, there is sexual dimorphism in MPS and its control in older adults; a greater basal rate of MPS, operating over most of the day may partially explain the slower loss of muscle in older women

Quality of life after carotid endarterectomy

<p>Abstract</p> <p>Background</p> <p>Most studies documenting beneficial outcomes after carotid endarterectomy (CE) are limited to mortality and morbidity rates, costs, and length of hospital stay (LOS). Few have examined the dependency of patients and how they perceive their own health changes after surgery. The aim of the present study was to evaluate quality of life and independence in activities of daily living (ADL) and to study its determinants.</p> <p>Methods</p> <p>Sixty-three patients admitted in the Post Anaesthesia Care Unit (PACU) after CE were eligible for this 14-month follow-up study. Patients were contacted 6 months after discharge to complete a Short Form-36 questionnaire (SF-36) and to have their dependency in ADL evaluated.</p> <p>Results</p> <p>Among 59 hospital survivors at 6 months follow-up, 43 completed the questionnaires. Sixty-three percent reported that their general level of health was better on the day they answered the questionnaire than 12 months earlier. Patients had worse SF-36 scores for all domains except bodily pain than a general urban population, and comparison with a group of patients 6 months after surgical ICU discharge showed no differences. Six months after PACU discharge, the Lawton Instrumental Activities of ADL Scale and the Katz Index of ADL demonstrated higher dependency scores (5.9 ± 2.2 versus 4.3 ± 2.4 and 0.3 ± 0.8 versus 0.6 ± 0.9, p < 0.001 and p = 0.047). Sixty-five percent and 33% were dependent in at least one activity in instrumental and personal ADL, respectively. Patients dependent in at least one ADL task had higher Revised Cardiac Risk Index (RCRI) scores (1.0 versus 1.5, p = 0.017). After controlling for multiple comparisons, no significant differences were found.</p> <p>Conclusion</p> <p>Patients undergoing CE have improved self-perception of quality of life despite being more dependent. Almost all their scores are worse than those in an urban population. We could identify no predictors of greater dependency in ADL tasks six months after PACU discharge.</p

Year in review in Intensive Care Medicine 2009: I. Pneumonia and infections, sepsis, outcome, acute renal failure and acid base, nutrition and glycaemic control

Journal ArticleReviewSCOPUS: re.jinfo:eu-repo/semantics/publishe

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

INTRODUCTION: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. METHODS: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. FINDINGS: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. INTERPRETATION: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification. FUNDING: UK Research and Innovation and National Institute for Health Research

Glutamate regulation of calcium and IP3 oscillating and pulsating dynamics in astrocytes

Recent years have witnessed an increasing interest in neuron-glia communication. This interest stems from the realization that glia participates in cognitive functions and information processing and is involved in many brain disorders and neurodegenerative diseases. An important process in neuron-glia communications is astrocyte encoding of synaptic information transfer: the modulation of intracellular calcium dynamics in astrocytes in response to synaptic activity. Here, we derive and investigate a concise mathematical model for glutamate-induced astrocytic intracellular Ca2+ dynamics that captures the essential biochemical features of the regulatory pathway of inositol 1,4,5-trisphosphate (IP3). Starting from the well-known two-state Li-Rinzel model for calcium-induced-calcium release, we incorporate the regulation of the IP3 production and phosphorylation. Doing so we extended it to a three-state model (referred as the G-ChI model), that could account for Ca2+ oscillations triggered by endogenous IP3 metabolism as well as by IP3 production by external glutamate signals. Compared to previous similar models, our three-state models include a more realistic description of the IP3 production and degradation pathways, lumping together their essential nonlinearities within a concise formulation. Using bifurcation analysis and time simulations, we demonstrate the existence of new putative dynamical features. The cross-couplings between IP3 and Ca2+ pathways endows the system with self-consistent oscillator properties and favor mixed frequency-amplitude encoding modes over pure amplitude modulation ones. These and additional results of our model are in general agreement with available experimental data and may have important implications on the role of astrocytes in the synaptic transfer of information.Comment: 42 pages, 16 figures, 1 table. Figure filenames mirror figure order in the paper. Ending "S" in figure filenames stands for "Supplementary Figure". This article was selected by the Faculty of 1000 Biology: "Genevieve Dupont: Faculty of 1000 Biology, 4 Sep 2009" at http://www.f1000biology.com/article/id/1163674/evaluatio