During the COVID-19 pandemic, the scarcity of resources has necessitated triage of critical care for patients with the disease. In patients aged 65 years and older, triage decisions are regularly ...based on degree of frailty measured by the Clinical Frailty Scale (CFS). However, the CFS could also be useful in patients younger than 65 years. We aimed to examine the association between CFS score and hospital mortality and between CFS score and admission to intensive care in adult patients of all ages with COVID-19 across Europe.
This analysis was part of the COVID Medication (COMET) study, an international, multicentre, retrospective observational cohort study in 63 hospitals in 11 countries in Europe. Eligible patients were aged 18 years and older, had been admitted to hospital, and either tested positive by PCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or were judged to have a high clinical likelihood of having SARS-CoV-2 infection by the local COVID-19 expert team. CFS was used to assess level of frailty: fit (CFS1–3), mildly frail (CFS4–5), or frail (CFS6–9). The primary outcome was hospital mortality. The secondary outcome was admission to intensive care. Data were analysed using a multivariable binary logistic regression model adjusted for covariates (age, sex, number of drugs prescribed, and type of drug class as a proxy for comorbidities).
Between March 30 and July 15, 2020, 2434 patients (median age 68 years IQR 55–77; 1480 61% men, 954 30% women) had CFS scores available and were included in the analyses. In the total sample and in patients aged 65 years and older, frail patients and mildly frail patients had a significantly higher risk of hospital mortality than fit patients (total sample: CFS6–9vs CFS1–3 odds ratio OR 2·71 95% CI 2·04–3·60, p<0·0001 and CFS4–5vs CFS1–3 OR 1·54 1·16–2·06, p=0·0030; age ≥65 years: CFS6–9vs CFS1–3 OR 2·90 2·12–3·97, p<0·0001 and CFS4–5vs CFS1–3 OR 1·64 1·20–2·25, p=0·0020). In patients younger than 65 years, an increased hospital mortality risk was only observed in frail patients (CFS6–9vs CFS1–3 OR 2·22 1·08–4·57, p=0·030; CFS4–5vs CFS1–3 OR 1·08 0·48–2·39, p=0·86). Frail patients had a higher incidence of admission to intensive care than fit patients (CFS6–9vs CFS1–3 OR 1·54 1·21–1·97, p=0·0010), whereas mildly frail patients had a lower incidence than fit patients (CFS4–5vs CFS1–3 OR 0·71 0·55–0·92, p=0·0090). Among patients younger than 65 years, frail patients had an increased incidence of admission to intensive care (CFS6–9vs CFS1–3 OR 2·96 1·98–4·43, p<0·0001), whereas mildly frail patients had no significant difference in incidence compared with fit patients (CFS4–5vs CFS1–3 OR 0·93 0·63–1·38, p=0·72). Among patients aged 65 years and older, frail patients had no significant difference in the incidence of admission to intensive care compared with fit patients (CFS6–9vs CFS1–3 OR 1·27 0·92–1·75, p=0·14), whereas mildly frail patients had a lower incidence than fit patients (CFS4–5vs CFS1–3 OR 0·66 0·47–0·93, p=0·018).
The results of this study suggest that CFS score is a suitable risk marker for hospital mortality in adult patients with COVID-19. However, treatment decisions based on the CFS in patients younger than 65 years should be made with caution.
LOEY Foundation.
In the PREPA observational study, we investigated the factors influencing pharmacokinetic and pharmacodynamic variability in the responses to fluindione, an oral anticoagulant drug, in a general ...population of octogenarian inpatients. Measurements of fluindione concentrations and international normalized ratio (INR) were obtained for 131 inpatients in whom fluindione treatment was initiated. Treatment was adjusted according to routine clinical practice. The data were analyzed using nonlinear mixed‐effects modeling, and the parameters were estimated using MONOLIX 3.2. The pharmacokinetics (PK) of fluindione was monocompartmental, whereas the evolution of INR was modeled in accordance with a turnover model (inhibition of vitamin K recycling). Interindividual variability (IIV) was very large. Clearance decreased with age and with prior administration of cordarone. Patients who had undergone surgery before the study had lower IC50 values, leading to an increased sensitivity to fluindione. Pharmacokinetic exposure is substantially increased in elderly patients, warranting a lower dose of fluindione.
Clinical Pharmacology & Therapeutics (2012); 91 5, 777–786. doi:10.1038/clpt.2011.309
Charmonia production at SPS energies Comets, M P
Journal of Physics G: Nuclear and Particle Physics,
12/2006, Letnik:
32, Številka:
12
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
J/ψ suppression in ultrarelativistic heavy-ion collisions has been predicted to be a signature of the transition from normal hadronic matter to a quark–gluon plasma. Several experiments have been ...devoted to charmonia production at the CERN/SPS: NA38, NA50 and NA60. All the results obtained so far in proton–proton, proton–nucleus and nucleus–nucleus collisions are summarized. Particular focus is dedicated to the proton–nucleus studies (and comparison to other experiments) needed to determine the normal nuclear absorption, knowledge of which is essential in order to extract the anomalous suppression obtained in nucleus–nucleus collisions.
We report a new measurement of J/ψ, ψ′ and Drell–Yan cross-sections, in the kinematical domain -0.425<ycm<0.575 and -0.5<cosθCS<0.5, performed at the CERN-SPS using 400 GeV/c incident protons on Be, ...Al, Cu, Ag, W and Pb targets. The dependence of the charmonia production cross-sections on the size of the target nucleus allows to quantify the so-called normal nuclear absorption. In the framework of the Glauber model, this new measurement is combined with results previously obtained with the same apparatus, under different experimental conditions, and leads to a precise determination of the J/ψ and ψ′ absorption cross-sections in the surrounding nuclear matter.
Measurements of midrapidity charged particle multiplicity distributions, $dN_{\rm ch}/d\eta$, and midrapidity transverse-energy distributions, $dE_T/d\eta$, are presented for a variety of collision ...systems and energies. Included are distributions for Au$+$Au collisions at $\sqrt{s_{_{NN}}}=200$, 130, 62.4, 39, 27, 19.6, 14.5, and 7.7 GeV, Cu$+$Cu collisions at $\sqrt{s_{_{NN}}}=200$ and 62.4 GeV, Cu$+$Au collisions at $\sqrt{s_{_{NN}}}=200$ GeV, U$+$U collisions at $\sqrt{s_{_{NN}}}=193$ GeV, $d$$+$Au collisions at $\sqrt{s_{_{NN}}}=200$ GeV, $^{3}$He$+$Au collisions at $\sqrt{s_{_{NN}}}=200$ GeV, and $p$$+$$p$ collisions at $\sqrt{s_{_{NN}}}=200$ GeV. Centrality-dependent distributions at midrapidity are presented in terms of the number of nucleon participants, $N_{\rm part}$, and the number of constituent quark participants, $N_{q{\rm p}}$. For all $A$$+$$A$ collisions down to $\sqrt{s_{_{NN}}}=7.7$ GeV, it is observed that the midrapidity data are better described by scaling with $N_{q{\rm p}}$ than scaling with $N_{\rm part}$. Also presented are estimates of the Bjorken energy density, $\varepsilon_{\rm BJ}$, and the ratio of $dE_T/d\eta$ to $dN_{\rm ch}/d\eta$, the latter of which is seen to be constant as a function of centrality for all systems.
ψ′ production is studied in Pb–Pb collisions at 158 GeV/c per nucleon incident momentum. Absolute cross-sections are measured and production rates are investigated as a function of the centrality of ...the collision. The results are compared with those obtained for lighter colliding systems and also for the J/ψ meson produced under identical conditions.
We present the first measurement of elliptic ($v_2$) and triangular ($v_3$) flow in high-multiplicity $^{3}$He$+$Au collisions at $\sqrt{s_{_{NN}}}=200$ GeV. Two-particle correlations, where the ...particles have a large separation in pseudorapidity, are compared in $^{3}$He$+$Au and in $p$$+$$p$ collisions and indicate that collective effects dominate the second and third Fourier components for the correlations observed in the $^{3}$He$+$Au system. The collective behavior is quantified in terms of elliptic $v_2$ and triangular $v_3$ anisotropy coefficients measured with respect to their corresponding event planes. The $v_2$ values are comparable to those previously measured in $d$$+$Au collisions at the same nucleon-nucleon center-of-mass energy. Comparison with various theoretical predictions are made, including to models where the hot spots created by the impact of the three $^{3}$He nucleons on the Au nucleus expand hydrodynamically to generate the triangular flow. The agreement of these models with data may indicate the formation of low-viscosity quark-gluon plasma even in these small collision systems.
COMET Phase-I technical design report Abramishvili, R; Adamov, G; Allin, A ...
Progress of theoretical and experimental physics,
03/2020, Letnik:
2020, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Abstract
The Technical Design for the COMET Phase-I experiment is presented in this paper. COMET is an experiment at J-PARC, Japan, which will search for neutrinoless conversion of muons into ...electrons in the field of an aluminum nucleus ($\mu$–$e$ conversion, $\mu^{-}N \rightarrow e^{-}N$); a lepton flavor-violating process. The experimental sensitivity goal for this process in the Phase-I experiment is $3.1\times10^{-15}$, or 90% upper limit of a branching ratio of $7\times 10^{-15}$, which is a factor of 100 improvement over the existing limit. The expected number of background events is 0.032. To achieve the target sensitivity and background level, the 3.2 kW 8 GeV proton beam from J-PARC will be used. Two types of detectors, CyDet and StrECAL, will be used for detecting the $\mu$–$e$ conversion events, and for measuring the beam-related background events in view of the Phase-II experiment, respectively. Results from simulation on signal and background estimations are also described.
Although infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has pleiotropic and systemic effects in some individuals
, many others experience milder symptoms. Here, to gain a ...more comprehensive understanding of the distinction between severe and mild phenotypes in the pathology of coronavirus disease 2019 (COVID-19) and its origins, we performed a whole-blood-preserving single-cell analysis protocol to integrate contributions from all major immune cell types of the blood-including neutrophils, monocytes, platelets, lymphocytes and the contents of the serum. Patients with mild COVID-19 exhibit a coordinated pattern of expression of interferon-stimulated genes (ISGs)
across every cell population, whereas these ISG-expressing cells are systemically absent in patients with severe disease. Paradoxically, individuals with severe COVID-19 produce very high titres of anti-SARS-CoV-2 antibodies and have a lower viral load compared to individuals with mild disease. Examination of the serum from patients with severe COVID-19 shows that these patients uniquely produce antibodies that functionally block the production of the ISG-expressing cells associated with mild disease, by activating conserved signalling circuits that dampen cellular responses to interferons. Overzealous antibody responses pit the immune system against itself in many patients with COVID-19, and perhaps also in individuals with other viral infections. Our findings reveal potential targets for immunotherapies in patients with severe COVID-19 to re-engage viral defence.
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