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

Association between components of the delirium syndrome and outcomes in hospitalised adults: a systematic review and meta-analysis.

BACKGROUND: Delirium is a heterogeneous syndrome with inattention as the core feature. There is considerable variation in the presence and degree of other symptom domains such as altered arousal, psychotic features and global cognitive dysfunction. Delirium is independently associated with increased mortality, but it is unclear whether individual symptom domains of delirium have prognostic importance. We conducted a systematic review and meta-analysis of studies in hospitalised adults in general settings to identify the relationship between symptom domains of delirium and outcomes. (PROSPERO: CRD42018093935). METHODS: We searched MEDLINE, EMBASE, PsycINFO, CINAHL, clinicaltrials.gov and the Cochrane Central Register of Controlled Trials from inception to November 2019. We included studies of hospitalised adults that reported associations between symptom domains of delirium and 30-day mortality (primary outcome), and other outcomes including mortality at other time points, length of stay, and dementia. Reviewer pairs independently screened articles, extracted data, and assessed risk of bias (Risk of Bias Assessment tool for Non-randomized Studies) and quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation framework. We performed random-effects meta-analyses stratified by delirium domain where possible. RESULTS: From 7092 citations we included 6 studies (6002 patients, 1112 with delirium). Higher mortality (ranging from in-hospital to follow-up beyond 12 months) was associated with altered arousal (pooled Odds Ratio (OR) 2.80, 95% Confidence Interval (CI) 2.33-3.37; moderate-quality evidence), inattention (pooled OR 2.57, 95% CI 1.74-3.80; low-quality evidence), and in single studies with disorientation, memory deficits and disorganised thoughts. Risk of bias varied across studies but was moderate-to-high overall, mainly due to selection bias, lack of blinding of assessments and unclear risk of selective outcome reporting. We found no studies on the association between psychotic features, visuospatial deficits or affective disturbances in delirium and outcomes, or studies reporting non-mortality outcomes. CONCLUSIONS: Few studies have related symptom domains of delirium to outcomes, but the available evidence suggests that altered arousal and inattention in delirium are associated with higher mortality than normal arousal and attention in people with or without delirium. Measurable symptom domains of delirium may have value in predicting survival and stratifying patients for treatment. We recommend that future delirium studies report outcomes by symptom domain

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

Late-onset erythromelalgia in a previously healthy young woman: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Erythromelalgia is a rare disorder characterized by episodic erythema and burning pain, which commonly involves the extremities. We present a case of late onset erythromelalgia in a previously healthy young woman and briefly review the literature. Our patient's case also has additional uncommon features not reported previously.</p> <p>Case presentation</p> <p>A 33-year-old previously healthy Caucasian woman presented with complaints of episodic burning pain and flushing occurring in a central distribution involving her face, ears, upper chest and, occasionally, her upper extremities. Her symptoms were triggered by lying down or warm temperature exposure and were relieved by cooling measures. Extensive diagnostic work-up looking for secondary causes for the symptoms was negative and the diagnosis of erythromelalgia was made based on details provided in her clinical history supported by raised temperature in the affected area measured by thermography during a symptomatic episode. The patient did not respond to pharmacological therapy or surgical sympathectomy. She was advised on lifestyle modification to avoid activities which triggered her symptoms. She was hypothermic with a core temperature between 92 and 95°F. She also had premature ovarian failure, which had not previously been reported.</p> <p>Conclusion</p> <p>Erythromelalgia is a rare disorder of unknown cause. There is no confirmatory diagnostic test; diagnosis is based on details provided in the patient's medical history and physical examination during the episodes. For those affected, this disorder leads to significant long-term morbidity and unfortunately, to date, no definitive therapy is available except for lifestyle modification.</p

Meningococcal genetic variation mechanisms viewed through comparative analysis of Serogroup C strain FAM18

Copyright @ 2007 Public Library of ScienceThe bacterium Neisseria meningitidis is commonly found harmlessly colonising the mucosal surfaces of the human nasopharynx. Occasionally strains can invade host tissues causing septicaemia and meningitis, making the bacterium a major cause of morbidity and mortality in both the developed and developing world. The species is known to be diverse in many ways, as a product of its natural transformability and of a range of recombination and mutation-based systems. Previous work on pathogenic Neisseria has identified several mechanisms for the generation of diversity of surface structures, including phase variation based on slippage-like mechanisms and sequence conversion of expressed genes using information from silent loci. Comparison of the genome sequences of two N. meningitidis strains, serogroup B MC58 and serogroup A Z2491, suggested further mechanisms of variation, including C-terminal exchange in specific genes and enhanced localised recombination and variation related to repeat arrays. We have sequenced the genome of N. meningitidis strain FAM18, a representative of the ST-11/ET-37 complex, providing the first genome sequence for the disease-causing serogroup C meningococci; it has 1,976 predicted genes, of which 60 do not have orthologues in the previously sequenced serogroup A or B strains. Through genome comparison with Z2491 and MC58 we have further characterised specific mechanisms of genetic variation in N. meningitidis, describing specialised loci for generation of cell surface protein variants and measuring the association between noncoding repeat arrays and sequence variation in flanking genes. Here we provide a detailed view of novel genetic diversification mechanisms in N. meningitidis. Our analysis provides evidence for the hypothesis that the noncoding repeat arrays in neisserial genomes (neisserial intergenic mosaic elements) provide a crucial mechanism for the generation of surface antigen variants. Such variation will have an impact on the interaction with the host tissues, and understanding these mechanisms is important to aid our understanding of the intimate and complex relationship between the human nasopharynx and the meningococcus.This work was supported by the Wellcome Trust through the Beowulf Genomics Initiative

A systematic review of studies reporting on neuropsychological and functional domains used for assessment of recovery from delirium in acute hospital patients

Objectives: Assessing for recovery in delirium is essential in guiding ongoing investigation and treatment. Yet, there is little scrutiny and no research or clinical consensus on how recovery should be measured. We reviewed studies which used tests of neuropsychological domains and functional ability to track recovery of delirium longitudinally in acute hospital settings. / Methods/Design: We systematically searched databases (MEDLINE, PsycInfo, CINAHL, Embase, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials), from inception to October 14th, 2022. Inclusion criteria were: adult acute hospital patients (≥18 years) diagnosed with delirium by a validated tool; 1+ repeat assessment using an assessment tool measuring domains of delirium/functional recovery ≤7 days from baseline. Two reviewers independently screened articles, performed data extraction, and assessed risk of bias. A narrative data synthesis was completed. / Results: From 6533 screened citations, we included 39 papers (reporting 32 studies), with 2370 participants with delirium. Studies reported 21 tools with an average of four repeat assessments including baseline (range 2–10 assessments within ≤7 days), measuring 15 specific domains. General cognition, functional ability, arousal, attention and psychotic features were most commonly assessed for longitudinal change. Risk of bias was moderate to high for most studies. / Conclusions: There was no standard approach for tracking change in specific domains of delirium. The methodological heterogeneity of studies was too high to draw firm conclusions on the effectiveness of assessment tools to measure delirium recovery. This highlights the need for standardised methods for assessing recovery from delirium

Functional traits of the world’s late Quaternary large-bodied avian and mammalian herbivores

Prehistoric and recent extinctions of large-bodied terrestrial herbivores had significant and lasting impacts on Earth’s ecosystems due to the loss of their distinct trait combinations. The world’s surviving large-bodied avian and mammalian herbivores remain among the most threatened taxa. As such, a greater understanding of the ecological impacts of large herbivore losses is increasingly important. However, comprehensive and ecologically-relevant trait datasets for extinct and extant herbivores are lacking. Here, we present HerbiTraits, a comprehensive functional trait dataset for all late Quaternary terrestrial avian and mammalian herbivores ≥10 kg (545 species). HerbiTraits includes key traits that influence how herbivores interact with ecosystems, namely body mass, diet, fermentation type, habitat use, and limb morphology. Trait data were compiled from 557 sources and comprise the best available knowledge on late Quaternary large-bodied herbivores. HerbiTraits provides a tool for the analysis of herbivore functional diversity both past and present and its effects on Earth’s ecosystems

The Effect of Selective Die Spacer Placement Techniques on the Seatability of Castings

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74992/1/j.1532-849X.1993.tb00382.x.pd

Onasemnogene abeparvovec preserves bulbar function in infants with presymptomatic spinal muscular atrophy: a post-hoc analysis of the SPR1NT trial

Bulbar function in spinal muscular atrophy has been defined as the ability to meet nutritional needs by mouth while maintaining airway protection and communicate verbally. The effects of disease-modifying treatment on bulbar function are not clear. A multidisciplinary team conducted post-hoc analyses of phase 3 SPR1NT trial data to evaluate bulbar function of infants at risk for spinal muscular atrophy who received one-time gene replacement therapy (onasemnogene abeparvovec) before symptom onset. Three endpoints represented adequate bulbar function in SPR1NT: (1) absence of physiologic swallowing impairment, (2) full oral nutrition, and (3) absence of adverse events indicating pulmonary instability. Communication was not assessed in SPR1NT. We descriptively assessed numbers/percentages of children who achieved each endpoint and all three collectively. SPR1NT included infants <6 postnatal weeks with two (n = 14) or three (n = 15) copies of the survival motor neuron 2 gene. At study end (18 [two-copy cohort] or 24 [three-copy cohort] months of age), 100% (29/29) of patients swallowed normally, achieved full oral nutrition, maintained pulmonary stability, and achieved the composite endpoint. When administered to infants before clinical symptom onset, onasemnogene abeparvovec allowed children at risk for spinal muscular atrophy to achieve milestones within published normal ranges of development and preserve bulbar function