Polypharmacy and emergency readmission to hospital after critical illness:a population-level cohort study

From PubMed via Jisc Publications RouterPolypharmacy is common and closely linked to drug interactions. The impact of polypharmacy has not been previously quantified in survivors of critical illness who have reduced resilience to stressors. Our aim was to identify factors associated with preadmission polypharmacy and ascertain whether polypharmacy is an independent risk factor for emergency readmission to hospital after discharge from a critical illness. A population-wide cohort study consisting of patients admitted to all Scottish general ICUs between January 1, 2011 and December 31, 2013, whom survived their ICU stay. Patients were stratified by presence of preadmission polypharmacy, defined as being prescribed five or more regular medications. The primary outcome was emergency hospital readmission within 1 yr of discharge from index hospital stay. Of 23 844 ICU patients, 29.9% were identified with polypharmacy (n=7138). Factors associated with polypharmacy included female sex, increasing age, and social deprivation. Emergency 1-yr hospital readmission was significantly higher in the polypharmacy cohort (51.8% vs 35.8%, P<0.001). After confounder adjustment, patients with polypharmacy had a 22% higher hazard of emergency 1-yr readmission (adjusted hazard ratio 1.22, 95% confidence interval 1.16-1.28, P<0.001). On a linear scale of polypharmacy each additional prescription conferred a 3% increase in hazard of emergency readmission by 1 yr (adjusted hazard ratio 1.03, 95% confidence interval 1.02-1.03, P<0.001). This national cohort study of ICU survivors demonstrates that preadmission polypharmacy is an independent risk factor for emergency readmission. In an ever-growing era of polypharmacy, this risk factor may represent a substantial burden in the at-risk post-intensive care population.126pubpub

Advances in optical sensing of explosive vapours

This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under agreement no 284747, and the EPSRC under EP/K503940/1, EP/K503162/1, and EP/N509759/1. IDWS acknowledges a Royal Society Wolfson Research Merit Award.Optical techniques for the detection of explosives are receiving increasing interest due to potentially fast responding, highly-sensitive systems. Conjugated polymers are suitable probe materials for this application since their fluorescence is quenched by electronegative materials including explosives. This can be used to make a sensor for explosive vapour, which can then give chemical information to help identify explosive devices, and complements other approaches such as metal detectors and ground penetrating radar. Whilst the principle has been known for some time, its practical implementation requires considerable development of instrumentation and materials, including preconcentration materials. This paper reports our current efforts to address these challenges, with particular emphasis on humanitarian demining and looking towards application in Improvised Explosive Device (IED) detection.Publisher PD

A portable, low-cost system for optical explosive detection based on a CMOS camera

Humanitarian demining requires a variety of methods and instrumentation for effective mine clearance, since a wide range of materials are used in mine manufacturing. However, landmines release vapours over time that can be detected, for example, by sniffer dogs. Optical sensor systems are especially suited to this application due to the potential for lightweight, portable, low-cost systems that nevertheless have fast response times and ppb-level sensitivity to explosive vapours. In this paper we present a system for detection based on a low-cost Raspberry Pi platform with an integrated CMOS camera. The conjugated polymers Super Yellow and Polyfluorene are excited by an LED, and the quenching effect by DNB vapour is monitored by the camera to indicate the presence of explosives. The system shows potential as a user friendly, lightweight platform for explosive vapour sensing.Publisher PD

Above–belowground herbivore interactions in mixed plant communities are influenced by altered precipitation patterns

Root- and shoot-feeding herbivores have the capacity to influence one another by modifying the chemistry of the shared host plant. This can alter rates of nutrient mineralization and uptake by neighboring plants and influence plant–plant competition, particularly in mixtures combining grasses and legumes. Root herbivory-induced exudation of nitrogen (N) from legume roots, for example, may increase N acquisition by co-occurring grasses, with knock-on effects on grassland community composition. Little is known about how climate change may affect these interactions, but an important and timely question is how will grass–legume mixtures respond in a future with an increasing reliance on legume N mineralization in terrestrial ecosystems. Using a model grass–legume mixture, this study investigated how simultaneous attack on lucerne (Medicago sativa) by belowground weevils (Sitona discoideus) and aboveground aphids (Acyrthosiphon pisum) affected a neighboring grass (Phalaris aquatica) when subjected to drought, ambient, and elevated precipitation. Feeding on rhizobial nodules by weevil larvae enhanced soil water retention under ambient and elevated precipitation, but only when aphids were absent. While drought decreased nodulation and root N content in lucerne, grass root and shoot chemistry were unaffected by changes in precipitation. However, plant communities containing weevils but not aphids showed increased grass height and N concentrations, most likely associated with the transfer of N from weevil-attacked lucerne plants containing more nodules and higher root N concentrations compared with insect-free plants. Drought decreased aphid abundance by 54% but increased total and some specific amino acid concentrations (glycine, lysine, methionine, tyrosine, cysteine, histidine, arginine, aspartate, and glutamate), suggesting that aphid declines were being driven by other facets of drought (e.g., reduced phloem hydraulics). The presence of weevil larvae belowground decreased aphid numbers by 30%, likely associated with a significant reduction in proline in weevil-treated lucerne plants. This study demonstrates how predicted changes to precipitation patterns and indirect interactions between herbivores can alter the outcome of competition between N-fixing legumes and non-N-fixing grasses, with important implications for plant community structure and productivity

The Effects of Age on Inflammatory and Coagulation-Fibrinolysis Response in Patients Hospitalized for Pneumonia

Objective: To determine whether inflammatory and hemostasis response in patients hospitalized for pneumonia varies by age and whether these differences explain higher mortality in the elderly. Methods: In an observational cohort of subjects with community-acquired pneumonia (CAP) recruited from emergency departments (ED) in 28 hospitals, we divided subjects into 5 age groups (85% subjects, older subjects had modestly increased hemostasis markers and IL-6 levels (p,0.01). Conclusions: Modest age-related increases in coagulation response occur during hospitalization for CAP; however these differences do not explain the large differences in mortality. Despite clinical recovery, immune resolution may be delayed in older adults at discharge. © 2010 Kale et al

The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC

Human leukocyte antigen alleles associate with COVID-19 vaccine immunogenicity and risk of breakthrough infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine immunogenicity varies between individuals, and immune responses correlate with vaccine efficacy. Using data from 1,076 participants enrolled in ChAdOx1 nCov-19 vaccine efficacy trials in the United Kingdom, we found that inter-individual variation in normalized antibody responses against SARS-CoV-2 spike and its receptor-binding domain (RBD) at 28 days after first vaccination shows genome-wide significant association with major histocompatibility complex (MHC) class II alleles. The most statistically significant association with higher levels of anti-RBD antibody was HLA-DQB1*06 (P = 3.2 × 10−9), which we replicated in 1,677 additional vaccinees. Individuals carrying HLA-DQB1*06 alleles were less likely to experience PCR-confirmed breakthrough infection during the ancestral SARS-CoV-2 virus and subsequent Alpha variant waves compared to non-carriers (hazard ratio = 0.63, 0.42–0.93, P = 0.02). We identified a distinct spike-derived peptide that is predicted to bind differentially to HLA-DQB1*06 compared to other similar alleles, and we found evidence of increased spike-specific memory B cell responses in HLA-DQB1*06 carriers at 84 days after first vaccination. Our results demonstrate association of HLA type with Coronavirus Disease 2019 (COVID-19) vaccine antibody response and risk of breakthrough infection, with implications for future vaccine design and implementation