The reaction
pp
→
pπ
+
X
was studied at three energies (
T
p
= 1520, 1805 and 2100 MeV). The analyzing powers of
p
p → ΔΔ,
p
p → Δn and
pp
→
pπ
+
X
reactions (0.94 <
M
X
< 1.5 GeV) were extracted ...between 0° and 17° in the lab, which corresponds to an angular range between 0° and 100° (c.m.). A theoretical analysis was performed based on s-channel contributions in 2
+ and 1
− intermediate states. The resulting formulas allow us to obtain good fits with experimental data.
Life-threatening "breakthrough" cases of critical COVID-19 are attributed to poor or waning antibody (Ab) response to SARS-CoV-2 vaccines in individuals already at risk. Preexisting auto-Abs ...neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; their contribution to hypoxemic breakthrough cases in vaccinated people is unknown. We studied a cohort of 48 individuals (aged 20 to 86 years) who received two doses of a messenger RNA (mRNA) vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Ab levels to the vaccine, neutralization of the virus, and auto-Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal Ab response to the vaccine. Among them, 10 (24%) had auto-Abs neutralizing type I IFNs (aged 43 to 86 years). Eight of these 10 patients had auto-Abs neutralizing both IFN-α2 and IFN-ω, whereas two neutralized IFN-ω only. No patient neutralized IFN-β. Seven neutralized type I IFNs at 10 ng/ml and three at 100 pg/ml only. Seven patients neutralized SARS-CoV-2 D614G and Delta efficiently, whereas one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only type I IFNs at 100 pg/ml neutralized both D614G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating Abs capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a notable proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population.
This study was designed to investigate the loss of well-being, in terms of life-years, overall and in patients randomized to metoprolol versus carvedilol in the Carvedilol Or Metoprolol European ...Trial (COMET).
The ultimate objectives of treating patients with heart failure are to relieve suffering and prolong life. Although the effect of treatment on mortality is usually described in trials, the effects on patient well-being throughout the trials' courses are rarely reported.
A total of 3,029 patients randomized in the COMET study were included in the analysis. "Patient journey" was calculated by adjusting days alive and out of hospital over four years using a five-point score completed by the patient every four months, adjusted according to the need for intensification of diuretic therapy. Scores ranged from 0% (dead or hospitalized) to 100% (feeling very well).
Over 48 months, 17% of all days were lost through death, 1% through hospitalization, 23% through impaired well-being, and 2% through the need for intensified therapy. Compared with metoprolol, carvedilol was associated with fewer days lost to death, with no increase in days lost due to impaired well-being or days in hospital. The "patient journey" score improved from a mean of 54.8% (SD 26.0) to 57.4% (SD 26.3%) (p < 0.0068).
Despite treatment with beta-blockers, heart failure remains associated with a marked reduction in well-being and survival. Loss of quality-adjusted life-years through death and poor well-being seemed of similar magnitude over four years, and both were much larger than the loss that could be attributed to hospitalization.
Background:
It is unclear whether beta-blocker therapy should be reduced or withdrawn in patients who develop acute decompensated heart failure (HF). We studied the relationship between changes in ...beta-blocker dose and outcome in patients surviving a HF hospitalisation in COMET.
Methods:
Patients hospitalised for HF were subdivided on the basis of the beta-blocker dose administered at the visit following hospitalisation, compared to that administered before.
Results:
In COMET, 752/3029 patients (25%, 361 carvedilol and 391 metoprolol) had a non-fatal HF hospitalisation while on study treatment. Of these, 61 patients (8%) had beta-blocker treatment withdrawn, 162 (22%) had a dose reduction and 529 (70%) were maintained on the same dose. One-and two-year cumulative mortality rates were 28.7% and 44.6% for patients withdrawn from study medication, 37.4% and 51.4% for those with a reduced dosage (n.s.) and 19.1% and 32.5% for those maintained on the same dose (HR,1.59; 95%CI, 1.28-1.98; p<0.001, compared to the others). The result remained significant in a multivariable model: (HR, 1.30; 95%CI, 1.02-1.66; p=0.0318). No interaction with the beneficial effects of carvedilol, compared to metoprolol, on outcome was observed (p=0.8436).
Conclusions:
HF hospitalisations are associated with a high subsequent mortality. The risk of death is higher in patients who discontinue beta-blocker therapy or have their dose reduced. The increase in mortality is only partially explained by the worse prognostic profile of these patients.
Charmonium suppression in Pb-Pb collisions at 158 GeV/c per nucleon is investigated in detail with the study of the transverse momentum distributions of J/
ψ as a function of the centrality of the ...collision. It is shown that the observed J/
ψ suppression in Pb-Pb interactions is particularly significant mainly at low transverse momentum where it strongly depends on centrality. For peripheral Pb-Pb collisions, the transverse momentum dependence of the J/
ψ cross section is, as a function of centrality, qualitatively similar to the dependence observed in p-A and S-U collisions. Comparing peripheral and central Pb-Pb collisions, the data show a relative suppression in the whole
p
T
range although its amplitude significantly decreases with increasing
p
T
and becomes almost
p
T
independent for the highest
p
T
values.
Abstract Background Uncertainty persists about the safety and efficacy of amiodarone for the management of heart failure. Methods and Results We randomized 3029 patients with chronic heart failure to ...receive carvedilol or metoprolol and followed patients for a median of 58 months. One hundred fifty-five of 1466 patients in New York Heart Association (NYHA) Class II and 209 of 1563 in Class III or IV received amiodarone at baseline. Persistence with amiodarone treatment was high and 66% received amiodarone after 4 years. During follow-up, 38.7% and 58.9% of patients receiving amiodarone in NYHA Classes II and III + IV died versus 26.2% and 43.3% not receiving amiodarone ( P < .001). This difference was maintained in multivariable analysis (hazard ratio HR 1.5, 95% confidence interval CI 1.2–1.7, P < .001). The difference was explained by an increased risk of death due to circulatory failure (HR 2.4, CI 1.9–3.1, P < .001) in patients receiving amiodarone. Sudden death was not different (HR 1.07, CI 0.8–1.4, P = .7). The increased risk was similar across NYHA classes with HR of 1.60 (CI 1.2–2.1, P < .001) in NYHA Class II versus 1.58 (CI 1.3–1.9, P < .001) in Classes III + IV. Conclusions Treatment with amiodarone was associated with an increased risk of death from circulatory failure independent of functional class.
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