Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a range of persistent symptoms impacting everyday functioning, known as post-COVID-19 condition or long ...COVID. We undertook a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks in non-hospitalized adults and the risk factors associated with developing persistent symptoms. We selected 486,149 adults with confirmed SARS-CoV-2 infection and 1,944,580 propensity score-matched adults with no recorded evidence of SARS-CoV-2 infection. Outcomes included 115 individual symptoms, as well as long COVID, defined as a composite outcome of 33 symptoms by the World Health Organization clinical case definition. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the outcomes. A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest aHRs were for anosmia (aHR 6.49, 95% CI 5.02-8.39), hair loss (3.99, 3.63-4.39), sneezing (2.77, 1.40-5.50), ejaculation difficulty (2.63, 1.61-4.28) and reduced libido (2.36, 1.61-3.47). Among the cohort of patients infected with SARS-CoV-2, risk factors for long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities. The risk of developing long COVID was also found to be increased along a gradient of decreasing age. SARS-CoV-2 infection is associated with a plethora of symptoms that are associated with a range of sociodemographic and clinical risk factors.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Conjugated polymer nanoparticles (CPNs) based on a common solar cell material (PTB7) have been prepared, and their potential in theranostic applications based on bioimaging and photosensitizing ...capabilities has been evaluated. The main absorption and emission bands of the prepared CPNs both fell within the NIR-I (650–950 nm) transparency window, allowing facile and efficient implementation of our CPNs as bioimaging agents, as demonstrated in this work for A549 human lung cancer cell cultures. The prepared CPN samples were also shown to produce reactive oxygen species (ROS) upon photoexcitation in the near-infrared or ultraviolet spectral regions, both in aqueous solutions and in HaCaT keratinocyte cell cultures. Importantly, we show that the photosensitizing ability of our CPNs was largely determined by the nature of the stabilizing shell: coating the CPNs with a Pluronic F-127 copolymer led to an improvement of photoinitiated ROS production, while using polystyrene-co-maleic anhydride instead completely quenched said process. This work therefore demonstrates that the photosensitizing capability of CPNs can be modulated via an appropriate selection of stabilizing material and highlights the significance of this parameter for the on-demand design of theranostic probes based on CPNs.
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IJS, KILJ, NUK, PNG, UL, UM
IntroductionIndividuals with COVID-19 frequently experience symptoms and impaired quality of life beyond 4–12 weeks, commonly referred to as Long COVID. Whether Long COVID is one or several distinct ...syndromes is unknown. Establishing the evidence base for appropriate therapies is needed. We aim to evaluate the symptom burden and underlying pathophysiology of Long COVID syndromes in non-hospitalised individuals and evaluate potential therapies.Methods and analysisA cohort of 4000 non-hospitalised individuals with a past COVID-19 diagnosis and 1000 matched controls will be selected from anonymised primary care records from the Clinical Practice Research Datalink, and invited by their general practitioners to participate on a digital platform (Atom5). Individuals will report symptoms, quality of life, work capability and patient-reported outcome measures. Data will be collected monthly for 1 year.Statistical clustering methods will be used to identify distinct Long COVID-19 symptom clusters. Individuals from the four most prevalent clusters and two control groups will be invited to participate in the BioWear substudy which will further phenotype Long COVID symptom clusters by measurement of immunological parameters and actigraphy.We will review existing evidence on interventions for postviral syndromes and Long COVID to map and prioritise interventions for each newly characterised Long COVID syndrome. Recommendations will be made using the cumulative evidence in an expert consensus workshop. A virtual supportive intervention will be coproduced with patients and health service providers for future evaluation.Individuals with lived experience of Long COVID will be involved throughout this programme through a patient and public involvement group.Ethics and disseminationEthical approval was obtained from the Solihull Research Ethics Committee, West Midlands (21/WM/0203). Research findings will be presented at international conferences, in peer-reviewed journals, to Long COVID patient support groups and to policymakers.Trial registration number1567490.
A survey of antibiotic stewardship programs was performed to determine essential resources. Increasing physician and pharmacist staffing support predicted effectiveness, and effectiveness was ...mediated by ability to perform antibiotic review with prospective audit and feedback. Recommended staffing ratios are provided.
Abstract
Background
Antibiotic stewardship programs improve clinical outcomes and patient safety and help combat antibiotic resistance. Specific guidance on resources needed to structure stewardship programs is lacking. This manuscript describes results of a survey of US stewardship programs and resultant recommendations regarding potential staffing structures in the acute care setting.
Methods
A cross-sectional survey of members of 3 infectious diseases subspecialty societies actively involved in antibiotic stewardship was conducted. Survey responses were analyzed with descriptive statistics. Logistic regression models were used to investigate the relationship between stewardship program staffing levels and self-reported effectiveness and to determine which strategies mediate effectiveness.
Results
Two-hundred forty-four respondents from a variety of acute care settings completed the survey. Prior authorization for select antibiotics, antibiotic reviews with prospective audit and feedback, and guideline development were common strategies. Eighty-five percent of surveyed programs demonstrated effectiveness in at least 1 outcome in the prior 2 years. Each 0.50 increase in pharmacist and physician full-time equivalent (FTE) support predicted a 1.48-fold increase in the odds of demonstrating effectiveness. The effect was mediated by the ability to perform prospective audit and feedback. Most programs noted significant barriers to success.
Conclusions
Based on our survey's results, we propose an FTE-to-bed ratio that can be used as a starting point to guide discussions regarding necessary resources for antibiotic stewardship programs with executive leadership. Prospective audit and feedback should be the cornerstone of stewardship programs, and both physician leadership and pharmacists with expertise in stewardship are crucial for success.
While evidence indicates that
(
) may promote colorectal carcinogenesis through its suppressive effect on T-cell-mediated antitumor immunity, the specific T-cell subsets involved remain uncertain.
We ...measured
DNA within tumor tissue by quantitative PCR on 933 cases (including 128
-positive cases) among 4,465 incident colorectal carcinoma cases in two prospective cohorts. Multiplex immunofluorescence combined with digital image analysis and machine learning algorithms for CD3, CD4, CD8, CD45RO (PTPRC isoform), and FOXP3 measured various T-cell subsets. We leveraged data on
, microsatellite instability (MSI), tumor whole-exome sequencing, and M1/M2-type tumor-associated macrophages TAM; by CD68, CD86, IRF5, MAF, and MRC1 (CD206) multimarker assay. Using the 4,465 cancer cases and inverse probability weighting method to control for selection bias due to tissue availability, multivariable-adjusted logistic regression analysis assessed the association between
and T-cell subsets.
The amount of
was inversely associated with tumor stromal CD3
lymphocytes multivariable OR, 0.47; 95% confidence interval (CI), 0.28-0.79, for
-high vs. -negative category;
= 0.0004 and specifically stromal CD3
CD4
CD45RO
cells (corresponding multivariable OR, 0.52; 95% CI, 0.32-0.85;
= 0.003). These relationships did not substantially differ by MSI status, neoantigen load, or exome-wide tumor mutational burden.
was not significantly associated with tumor intraepithelial T cells or with M1 or M2 TAMs.
The amount of tissue
is associated with lower density of stromal memory helper T cells. Our findings provide evidence for the interactive pathogenic roles of microbiota and specific immune cells.
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