119 research outputs found
Haloperidol and Ziprasidone for Treatment of Delirium in Critical Illness
BACKGROUND:
There are conflicting data on the effects of antipsychotic medications on delirium in patients in the intensive care unit (ICU).
METHODS:
In a randomized, double-blind, placebo-controlled trial, we assigned patients with acute respiratory failure or shock and hypoactive or hyperactive delirium to receive intravenous boluses of haloperidol (maximum dose, 20 mg daily), ziprasidone (maximum dose, 40 mg daily), or placebo. The volume and dose of a trial drug or placebo was halved or doubled at 12-hour intervals on the basis of the presence or absence of delirium, as detected with the use of the Confusion Assessment Method for the ICU, and of side effects of the intervention. The primary end point was the number of days alive without delirium or coma during the 14-day intervention period. Secondary end points included 30-day and 90-day survival, time to freedom from mechanical ventilation, and time to ICU and hospital discharge. Safety end points included extrapyramidal symptoms and excessive sedation.
RESULTS:
Written informed consent was obtained from 1183 patients or their authorized representatives. Delirium developed in 566 patients (48%), of whom 89% had hypoactive delirium and 11% had hyperactive delirium. Of the 566 patients, 184 were randomly assigned to receive placebo, 192 to receive haloperidol, and 190 to receive ziprasidone. The median duration of exposure to a trial drug or placebo was 4 days (interquartile range, 3 to 7). The median number of days alive without delirium or coma was 8.5 (95% confidence interval [CI], 5.6 to 9.9) in the placebo group, 7.9 (95% CI, 4.4 to 9.6) in the haloperidol group, and 8.7 (95% CI, 5.9 to 10.0) in the ziprasidone group (P=0.26 for overall effect across trial groups). The use of haloperidol or ziprasidone, as compared with placebo, had no significant effect on the primary end point (odds ratios, 0.88 [95% CI, 0.64 to 1.21] and 1.04 [95% CI, 0.73 to 1.48], respectively). There were no significant between-group differences with respect to the secondary end points or the frequency of extrapyramidal symptoms.
CONCLUSIONS:
The use of haloperidol or ziprasidone, as compared with placebo, in patients with acute respiratory failure or shock and hypoactive or hyperactive delirium in the ICU did not significantly alter the duration of delirium. (Funded by the National Institutes of Health and the VA Geriatric Research Education and Clinical Center; MIND-USA ClinicalTrials.gov number, NCT01211522 .)
Measurements of long-range near-side angular correlations in TeV proton-lead collisions in the forward region
Two-particle angular correlations are studied in proton-lead collisions at a
nucleon-nucleon centre-of-mass energy of TeV, collected
with the LHCb detector at the LHC. The analysis is based on data recorded in
two beam configurations, in which either the direction of the proton or that of
the lead ion is analysed. The correlations are measured in the laboratory
system as a function of relative pseudorapidity, , and relative
azimuthal angle, , for events in different classes of event
activity and for different bins of particle transverse momentum. In
high-activity events a long-range correlation on the near side, , is observed in the pseudorapidity range . This
measurement of long-range correlations on the near side in proton-lead
collisions extends previous observations into the forward region up to
. The correlation increases with growing event activity and is found
to be more pronounced in the direction of the lead beam. However, the
correlation in the direction of the lead and proton beams are found to be
compatible when comparing events with similar absolute activity in the
direction analysed.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-040.htm
Study of the production of and hadrons in collisions and first measurement of the branching fraction
The product of the () differential production
cross-section and the branching fraction of the decay () is
measured as a function of the beauty hadron transverse momentum, ,
and rapidity, . The kinematic region of the measurements is and . The measurements use a data sample
corresponding to an integrated luminosity of collected by the
LHCb detector in collisions at centre-of-mass energies in 2011 and in 2012. Based on previous LHCb
results of the fragmentation fraction ratio, , the
branching fraction of the decay is
measured to be \begin{equation*} \mathcal{B}(\Lambda_b^0\rightarrow J/\psi
pK^-)= (3.17\pm0.04\pm0.07\pm0.34^{+0.45}_{-0.28})\times10^{-4},
\end{equation*} where the first uncertainty is statistical, the second is
systematic, the third is due to the uncertainty on the branching fraction of
the decay , and the
fourth is due to the knowledge of . The sum of the
asymmetries in the production and decay between and
is also measured as a function of and .
The previously published branching fraction of , relative to that of , is updated.
The branching fractions of are determined.Comment: 29 pages, 19figures. All figures and tables, along with any
supplementary material and additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-032.htm
Evidence for the strangeness-changing weak decay
Using a collision data sample corresponding to an integrated luminosity
of 3.0~fb, collected by the LHCb detector, we present the first search
for the strangeness-changing weak decay . No
hadron decay of this type has been seen before. A signal for this decay,
corresponding to a significance of 3.2 standard deviations, is reported. The
relative rate is measured to be
, where and
are the and fragmentation
fractions, and is the branching
fraction. Assuming is bounded between 0.1 and
0.3, the branching fraction would lie
in the range from to .Comment: 7 pages, 2 figures, All figures and tables, along with any
supplementary material and additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-047.htm
Chronic neuropsychiatric sequelae of SARSâCoVâ2: Protocol and methods from the Alzheimer's Association Global Consortium
Introduction
Coronavirus disease 2019 (COVID-19) has caused >3.5 million deaths worldwide and affected >160 million people. At least twice as many have been infected but remained asymptomatic or minimally symptomatic. COVID-19 includes central nervous system manifestations mediated by inflammation and cerebrovascular, anoxic, and/or viral neurotoxicity mechanisms. More than one third of patients with COVID-19 develop neurologic problems during the acute phase of the illness, including loss of sense of smell or taste, seizures, and stroke. Damage or functional changes to the brain may result in chronic sequelae. The risk of incident cognitive and neuropsychiatric complications appears independent from the severity of the original pulmonary illness. It behooves the scientific and medical community to attempt to understand the molecular and/or systemic factors linking COVID-19 to neurologic illness, both short and long term.
Methods
This article describes what is known so far in terms of links among COVID-19, the brain, neurological symptoms, and Alzheimer's disease (AD) and related dementias. We focus on risk factors and possible molecular, inflammatory, and viral mechanisms underlying neurological injury. We also provide a comprehensive description of the Alzheimer's Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2) harmonized methodology to address these questions using a worldwide network of researchers and institutions.
Results
Successful harmonization of designs and methods was achieved through a consensus process initially fragmented by specific interest groups (epidemiology, clinical assessments, cognitive evaluation, biomarkers, and neuroimaging). Conclusions from subcommittees were presented to the whole group and discussed extensively. Presently data collection is ongoing at 19 sites in 12 countries representing Asia, Africa, the Americas, and Europe.
Discussion
The Alzheimer's Association Global Consortium harmonized methodology is proposed as a model to study long-term neurocognitive sequelae of SARS-CoV-2 infection
Measurement of CP observables in B± â D(â)K± and B± â D(â)ϱ decays
Measurements of CP observables in B ± âD (â) K ± and B ± âD (â) Ï Â± decays are presented, where D (â) indicates a neutral D or D â meson that is an admixture of D (â)0 and DÂŻ (â)0 states. Decays of the D â meson to the DÏ 0 and DÎł final states are partially reconstructed without inclusion of the neutral pion or photon, resulting in distinctive shapes in the B candidate invariant mass distribution. Decays of the D meson are fully reconstructed in the K ± Ï â , K + K â and Ï + Ï â final states. The analysis uses a sample of charged B mesons produced in pp collisions collected by the LHCb experiment, corresponding to an integrated luminosity of 2.0, 1.0 and 2.0 fb â1 taken at centre-of-mass energies of s=7, 8 and 13 TeV, respectively. The study of B ± âD â K ± and B ± âD â Ï Â± decays using a partial reconstruction method is the first of its kind, while the measurement of B ± âDK ± and B ± âDÏ Â± decays is an update of previous LHCb measurements. The B ± âDK ± results are the most precise to date
Risk factors and outcomes associated with recurrent autoimmune hepatitis following liver transplantation
Background & Aims: Autoimmune hepatitis can recur after liver transplantation (LT), though the impact of recurrence on patient and graft survival has not been well characterized. We evaluated a large, international, multicenter cohort to identify the probability and risk factors associated with recurrent AIH and the association between recurrent disease and patient and graft survival.Methods: We included 736 patients (77% female, mean age 42 +/- 1 years) with AIH who underwent LT from January 1987 through June 2020, among 33 centers in North America, South America, Europe and Asia. Clinical data before and after LT, biochemical data within the first 12 months after LT, and immunosuppression after LT were analyzed to identify patients at higher risk of AIH recurrence based on histological diagnosis.Results: AIH recurred in 20% of patients after 5 years and 31% after 10 years. Age at LT <= 42 years (hazard ratio [HR] 3.15; 95% CI 1.22-8.16; p = 0.02), use of mycophenolate mofetil post-LT (HR 3.06; 95% CI 1.39-6.73; p = 0.005), donor and recipient sex mismatch (HR 2.57; 95% CI 1.39-4.76; p = 0.003) and high IgG pre-LT (HR 1.04; 95% CI 1.01-1.06; p = 0.004) were associated with higher risk of AIH recurrence after adjusting for other confounders. In multivariate Cox regression, recurrent AIH (as a time-dependent covariate) was significantly associated with graft loss (HR 10.79, 95% CI 5.37-21.66, p <0.001) and death (HR 2.53, 95% CI 1.48-4.33, p = 0.001).Conclusion: Recurrence of AIH following transplant is frequent and is associated with younger age at LT, use of mycophenolate mofetil post-LT, sex mismatch and high IgG pre-LT. We demonstrate an association between disease recurrence and impaired graft and overall survival in patients with AIH, highlighting the importance of ongoing efforts to better characterize, prevent and treat recurrent AIH.Lay summary: Recurrent autoimmune hepatitis following liver transplant is frequent and is associated with some recipient features and the type of immunosuppressive medications use. Recurrent autoimmune hepatitis negatively affects outcomes after liver transplantation. Thus, improved measures are required to prevent and treat this condition. (C) 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.Cellular mechanisms in basic and clinical gastroenterology and hepatolog
Model-independent measurement of mixing parameters in Dââ K ÏÏ decays
The first model-independent measurement of the charm mixing parameters in the
decay is reported, using a sample of collision
data recorded by the LHCb experiment, corresponding to an integrated luminosity
of 1.0 fb at a centre-of-mass energy of 7 TeV. The measured values are
\begin{eqnarray*} x &=& (-0.86 \pm 0.53 \pm 0.17) \times 10^{-2}, \\ y &=&
(+0.03 \pm 0.46 \pm 0.13) \times 10^{-2}, \end{eqnarray*} where the first
uncertainties are statistical and include small contributions due to the
external input for the strong phase measured by the CLEO collaboration, and the
second uncertainties are systematic.Comment: 25 pages, 3 figures. Sign error in x fixed as of v2. All figures and
tables, along with any supplementary material and additional information, are
available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-042.htm
Measurement of asymmetries in and decays
See paper for full list of authors - All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-041.html - Submitted to Phys. Lett. BInternational audienceA search for CP violation in D±âηâČϱ and D±sâηâČϱ decays is performed using proton-proton collision data, corresponding to an integrated luminosity of 3 fbâ1, recorded by the LHCb experiment at centre-of-mass energies of 7 and 8 TeV. The measured CP-violating charge asymmetries are ACP(D±âηâČϱ)=(â0.61±0.72±0.55±0.12)% and ACP(D±sâηâČϱ)=(â0.82±0.36±0.24±0.27)%, where the first uncertainties are statistical, the second systematic, and the third are the uncertainties on the ACP(D±âK0Sϱ) and ACP(D±sâÏϱ) measurements used for calibration. The results represent the most precise measurements of these asymmetries to date
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