Do specific delirium aetiologies have different associations with death? A longitudinal cohort of hospitalised patients

PURPOSE: To describe aetiology-specific associations with mortality among older hospital patients with delirium. METHODS: Over 21 months, a cohort of 1702 patients with 2471 acute hospital admissions (median age 85, IQR 80-90, 56% women) were assessed for delirium, categorised with inflammatory and metabolic aetiologies based on available laboratory results, and followed up for all-cause mortality. Interactions between aetiology and delirium were tested. RESULTS: The total mortality for the cohort was 35.2%. While inflammation, metabolic disturbance, and delirium at time of admission all demonstrated independent associations with mortality, there was no evidence for any interactions between delirium and these laboratory-measured aetiologies. CONCLUSIONS: Delirium remains an important predictor of death in older hospital patients, irrespective of underlying aetiology

The relative impact of socioeconomic position and frailty varies by population setting

INTRODUCTION: Frailty and socioeconomic position (SEP) are well-established determinants of health. However, we know less about the contributions of frailty and SEP in older adults, especially in acute settings. We set out to answer how frailty and SEP might influence health outcomes in older people, comparing a population sample and patients managed by a speciality acute frailty service. METHODS: We used the Delirium and Population Health Informatics Cohort, a population sample of 1510 individuals aged ≥70 years from the London Borough of Camden and 1750 acute frailty patients. SEP was determined using the Index of Multiple Deprivation. Linear and Cox proportional hazard regression models were conducted to assess SEP on frailty, readmission, and mortality outcomes. RESULTS: In the population sample, SEP was significantly associated with frailty and mortality with successive increases in rate of death for each IMD quintile (HR = 1.28, 95% CI 1.11 to 1.49, P < 0.005). Increasing SEP, age, and admission status among hospitalized individuals were associated with greater frailty. For individuals seen by the speciality frailty service, SEP was not associated with frailty, mortality, or readmission. DISCUSSION: When older people experience acute illness severe enough to require secondary care, particularly specialist services, this overcomes any prior advantages conferred by a higher SEP

Complementing chronic frailty assessment at hospital admission with an electronic frailty index (FI-Laboratory) comprising routine blood test results

BACKGROUND: Acutely ill and frail older adults have complex social and health care needs. It is important to understand how this complexity affects acute outcomes for admission to hospital. We validated a frailty index using routine admission laboratory tests with outcomes after patients were admitted to hospital. METHODS: In a prospective cohort of older adults admitted to a large tertiary hospital in the United Kingdom, we created a frailty index from routine admission laboratory investigations (FI-Laboratory) linked to data comprising hospital outcomes. We evaluated the association between the FI-Laboratory and total days spent in hospital, discharge to a higher level of care, readmission and mortality. RESULTS: Of 2552 admissions among 1750 older adults, we were able to generate FI-Laboratory values for 2254 admissions (88.3% of the cohort). More than half of admitted patients were women (55.3%) and the mean age was 84.6 (SD 14.0) years. We found that the FI-Laboratory correlated weakly with the Clinical Frailty Scale (CFS; r2 = 0.09). An increase in the CFS and the equivalent of 3 additional abnormal laboratory test results in the FI-Laboratory, respectively, were associated with an increased proportion of inpatient days (rate ratios [RRs] 1.43, 95% confidence interval [CI] 1.35-1.52; and 1.47, 95% CI 1.41-1.54), discharge to a higher level of care (odd ratios [ORs] 1.39, 95% CI 1.27-1.52; and 1.30, 95% CI 1.16-1.47) and increased readmission rate (hazard ratios [HRs] 1.26, 95% CI 1.17-1.37; and 1.18, 95% CI 1.11-1.26). Increases in the CFS and FI-Laboratory were associated with increased mortality HRs of 1.39 (95% CI 1.28-1.51) and 1.45 (95% CI 1.37-1.54), respectively. INTERPRETATION: We determined that FI-Laboratory, distinct from baseline frailty, could be used to predict risk of many adverse outcomes. The score is therefore a useful way to quantify the degree of acute illness in frail older adults

Clinical outcomes in patients with atrial fibrillation and frailty: insights from the ENGAGE AF-TIMI 48 trial

Background Atrial fibrillation (AF) is common in older people with frailty and is associated with an increased risk of stroke and systemic embolism. Whilst oral anticoagulation is associated with a reduction in this risk, there is a lack of data on the safety and efficacy of direct oral anticoagulants (DOACs) in people with frailty. This study aims to report clinical outcomes of patients with AF in the Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) trial by frailty status. Methods Post hoc analysis of 20,867 participants in the ENGAGE AF-TIMI 48 trial, representing 98.8% of those randomised. This double-blinded double-dummy trial compared two once-daily regimens of edoxaban (a DOAC) with warfarin. Participants were categorised as fit, living with pre-frailty, mild-moderate, or severe frailty according to a standardised index, based upon the cumulative deficit model. The primary efficacy endpoint was stroke or systemic embolism and the safety endpoint was major bleeding. Results A fifth (19.6%) of the study population had frailty (fit: n = 4459, pre-frailty: n = 12,326, mild-moderate frailty: n = 3722, severe frailty: n = 360). On average over the follow-up period, the risk of stroke or systemic embolism increased by 37% (adjusted HR 1.37, 95% CI 1.19–1.58) and major bleeding by 42% (adjusted HR 1.42, 1.27–1.59) for each 0.1 increase in the frailty index (four additional health deficits). Edoxaban was associated with similar efficacy to warfarin in every frailty category, and a lower risk of bleeding than warfarin in all but those living with severe frailty. Conclusions Edoxaban was similarly efficacious to warfarin across the frailty spectrum and was associated with lower rates of bleeding except in those with severe frailty. Overall, with increasing frailty, there was an increase in stroke and bleeding risk. There is a need for high-quality, frailty-specific population randomised control trials to guide therapy in this vulnerable population. Trial registration ClinicalTrials.gov NCT00781391. First registered on 28 October 200

Star forming dwarf galaxies

Star forming dwarf galaxies (SFDGs) have a high gas content and low metallicities, reminiscent of the basic entities in hierarchical galaxy formation scenarios. In the young universe they probably also played a major role in the cosmic reionization. Their abundant presence in the local volume and their youthful character make them ideal objects for detailed studies of the initial stellar mass function (IMF), fundamental star formation processes and its feedback to the interstellar medium. Occasionally we witness SFDGs involved in extreme starbursts, giving rise to strongly elevated production of super star clusters and global superwinds, mechanisms yet to be explored in more detail. SFDGs is the initial state of all dwarf galaxies and the relation to the environment provides us with a key to how different types of dwarf galaxies are emerging. In this review we will put the emphasis on the exotic starburst phase, as it seems less important for present day galaxy evolution but perhaps fundamental in the initial phase of galaxy formation.Comment: To appear in JENAM Symposium "Dwarf Galaxies: Keys to Galaxy Formation and Evolution", P. Papaderos, G. Hensler, S. Recchi (eds.). Lisbon, September 2010, Springer Verlag, in pres

Prevalence and correlates of frailty in an older rural African population:findings from the HAALSI cohort study

Background: Frailty is a key predictor of death and dependency, yet little is known about frailty in sub-Saharan Africa despite rapid population ageing. We describe the prevalence and correlates of phenotypic frailty using data from the Health and Aging in Africa: Longitudinal Studies of an INDEPTH Community cohort. Methods: We analysed data from rural South Africans aged 40 and over. We used low grip strength, slow gait speed, low body mass index, and combinations of self-reported exhaustion, decline in health, low physical activity and high self-reported sedentariness to derive nine variants of a phenotypic frailty score. Each frailty category was compared with self-reported health, subjective wellbeing, impairment in activities of daily living and the presence of multimorbidity. Cox regression analyses were used to compare subsequent all-cause mortality for non-frail (score 0), pre-frail (score 1–2) and frail participants (score 3+). Results: Five thousand fifty nine individuals (mean age 61.7 years, 2714 female) were included in the analyses. The nine frailty score variants yielded a range of frailty prevalences (5.4% to 13.2%). For all variants, rates were higher in women than in men, and rose steeply with age. Frailty was associated with worse subjective wellbeing, and worse self-reported health. Both prefrailty and frailty were associated with a higher risk of death during a mean 17 month follow up for all score variants (hazard ratios 1.29 to 2.41 for pre-frail vs non-frail; hazard ratios 2.65 to 8.91 for frail vs non-frail). Conclusions: Phenotypic frailty could be measured in this older South African population, and was associated with worse health, wellbeing and earlier death

Vernalization-Repression of Arabidopsis FLC Requires Promoter Sequences but Not Antisense Transcripts

The repression of Arabidopsis FLC expression by vernalization (extended cold) has become a model for understanding polycomb-associated epigenetic regulation in plants. Antisense and sense non-coding RNAs have been respectively implicated in initiation and maintenance of FLC repression by vernalization. We show that the promoter and first exon of the FLC gene are sufficient to initiate repression during vernalization; this initial repression of FLC does not require antisense transcription. Long-term maintenance of FLC repression requires additional regions of the gene body, including those encoding sense non-coding transcripts

The frailty index outperforms DNA methylation age and its derivatives as an indicator of biological age

The measurement of biological age as opposed to chronological age is important to allow the study of factors that are responsible for the heterogeneity in the decline in health and function ability among individuals during aging. Various measures of biological aging have been proposed. Frailty indices based on health deficits in diverse body systems have been well studied, and we have documented the use of a frailty index (FI(34)) composed of 34 health items, for measuring biological age. A different approach is based on leukocyte DNA methylation. It has been termed DNA methylation age, and derivatives of this metric called age acceleration difference and age acceleration residual have also been employed. Any useful measure of biological age must predict survival better than chronological age does. Meta-analyses indicate that age acceleration difference and age acceleration residual are significant predictors of mortality, qualifying them as indicators of biological age. In this article, we compared the measures based on DNA methylation with FI(34). Using a well-studied cohort, we assessed the efficiency of these measures side by side in predicting mortality. In the presence of chronological age as a covariate, FI(34) was a significant predictor of mortality, whereas none of the DNA methylation age-based metrics were. The outperformance of FI(34) over DNA methylation age measures was apparent when FI(34) and each of the DNA methylation age measures were used together as explanatory variables, along with chronological age: FI(34) remained significant but the DNA methylation measures did not. These results indicate that FI(34) is a robust predictor of biological age, while these DNA methylation measures are largely a statistical reflection of the passage of chronological time

Human–agent collaboration for disaster response

In the aftermath of major disasters, first responders are typically overwhelmed with large numbers of, spatially distributed, search and rescue tasks, each with their own requirements. Moreover, responders have to operate in highly uncertain and dynamic environments where new tasks may appear and hazards may be spreading across the disaster space. Hence, rescue missions may need to be re-planned as new information comes in, tasks are completed, or new hazards are discovered. Finding an optimal allocation of resources to complete all the tasks is a major computational challenge. In this paper, we use decision theoretic techniques to solve the task allocation problem posed by emergency response planning and then deploy our solution as part of an agent-based planning tool in real-world field trials. By so doing, we are able to study the interactional issues that arise when humans are guided by an agent. Specifically, we develop an algorithm, based on a multi-agent Markov decision process representation of the task allocation problem and show that it outperforms standard baseline solutions. We then integrate the algorithm into a planning agent that responds to requests for tasks from participants in a mixed-reality location-based game, called AtomicOrchid, that simulates disaster response settings in the real-world. We then run a number of trials of our planning agent and compare it against a purely human driven system. Our analysis of these trials show that human commanders adapt to the planning agent by taking on a more supervisory role and that, by providing humans with the flexibility of requesting plans from the agent, allows them to perform more tasks more efficiently than using purely human interactions to allocate tasks. We also discuss how such flexibility could lead to poor performance if left unchecked