Notes

The particular spliceosome pathway activity correlates with reduced anti-tumor defenses as well as immunotherapy response, and bad medical results within pan-cancer.
Governmental agencies (US Food and Drug Administration and European Medicines Agency) implemented initiatives to improve pediatric clinical research, starting in 1997 and 2007, respectively. The aim of this review was to quantify the unlicensed and off-label drug uses in children before and after these implementations.

Literature review of unlicensed and off-label drug uses was performed on PubMed and Google-Scholar from 1985 to 2014. Relevant titles/abstracts were reviewed, and articles were included if evaluating unlicensed/off-label drug uses, with a clear description of health care setting and studied population. Included articles were divided into 3 groups studies conducted in United States (before/after 2007), in Europe (before/after 2007), and in other countries.

Of the 48 articles reviewed, 27 were included. Before implementation of pediatric initiatives, global unlicensed drug use rate in Europe was found to be 0.2% to 36% for inpatients and 0.3% to 16.6% for outpatients. After implementation, it marginally decreased to 11.4% and 1.26% to 6.7%, respectively. Concerning off-label drug use rates, it was found to be 18% to 66% for inpatients and 10.5% to 37.5% for outpatients before the implementation. After implementation, it decreased marginally to 33.2% to 46.5% and to 3.3% to 13.5%, respectively. In other countries, unlicensed and off-label drug use rates were found to be, respectively, 8% to 27.3% and 11% to 47%.

Governmental initiatives to improve clinical research conducted in children seem to have had a marginal effect to decrease the unlicensed and off-label drug uses prevalence in Europe.
Governmental initiatives to improve clinical research conducted in children seem to have had a marginal effect to decrease the unlicensed and off-label drug uses prevalence in Europe.
Emergency department (ED) providers are faced with the challenge of diagnosing and treating patients in a timely fashion given many obstacles including limited patient information, complex disease states, and high patient turnover. Time delays in administration or selection of appropriate drug therapies have been associated with negative outcomes in severe infections. This study was conducted to assess the impact of an emergency medicine pharmacist (EPh) on the selection of appropriate antibiotics and the timeliness of administration in pediatric patients in the ED.

Patients younger than 18 years were evaluated who were admitted through the ED and received 1 dose of intravenous antibiotic for the following conditions community-acquired pneumonia, complicated skin and soft tissue infection (SSTI), meningitis, and sepsis. To evaluate the impact of the presence of an EPh, patients with orders placed during the EPh's hours of 1 pm and 11 pm were compared to those with an order placed between 11 pm and 1 pm.

the EPh is present. Areas for future investigation include whether the presence of EPhs at the bedside has the potential to impact areas of patient care, including readmission rates, drug costs, and medication errors.
To describe current opinions about stress-related mucosal disease (SRMD) prevention in Canadian pediatric intensive care units (PICUs).

A 22-question survey covering several aspects of SRMD was sent to all identified PICU attendings in Canada.

Sixty-eight percent of identified attendings completed the questionnaire. Thirty-eight percent were based in Quebec, 31% in Alberta, and 31% from other provinces. Most attendings (78%) had worked in a PICU for 6 years or more. When asked about risk factors for prescribing SRMD prevention drugs (more than 1 answer was accepted), the most popular answers were prior history of gastric ulceration/bleeding (33 respondents), coagulopathy (28 respondents), and major neurologic insult (18 respondents). Almost half of the attendings (48%) mentioned that they prescribe SRMD prophylaxis directly upon PICU admission to more than 25% of their patients. Forty-nine percent of respondents subjectively estimated that clinically significant upper gastrointestinal bleeding (UGIB; defined as UGIB associated with either hypotension, transfusion within 24 hours of the event, or death) occurred in less than 1% of their patients. Fifty-seven respondents (93%) used ranitidine as first-line therapy (average dose 4.1 mg/kg/day, mainly intravenously). As second-line therapy, 32 attendings (52%) used pantoprazole and 13 (21%) used omeprazole.

Despite the paucity of guidelines on SRMD prevention and the low reported incidence of clinically significant UGIB, SRMD prevention is frequently used in Canadian PICUs. Ranitidine is the first-line drug used by most attendings.
Despite the paucity of guidelines on SRMD prevention and the low reported incidence of clinically significant UGIB, SRMD prevention is frequently used in Canadian PICUs. Ranitidine is the first-line drug used by most attendings.
With increasing complexity of critical care medicine comes an increasing need for multidisciplinary involvement in care. In many institutions, pharmacists are an integral part of this team, but long-term data on the interventions performed by pharmacists and their effects on patient care and outcomes are limited. We aimed to describe the role of pediatric clinical pharmacists in pediatric intensive care unit (PICU) practice.

We retrospectively reviewed the records of pharmacy interventions in the PICU at the Mayo Clinic in Rochester, Minnesota, from 2003-2013, with a distinct period of increased pharmacist presence in the PICU from 2008 onward. We compared demographic and outcome data on patients who did and who did not have pharmacy interventions during 2 periods (2003-2007 and 2008-2013).

We identified 27,773 total interventions by pharmacists during the 11-year period, of which 79.8% were accepted by the clinical team. These interventions were made on 10,963 unique PICU admissions and prevented 5867 order entry errors. see more Pharmacists' interventions increased year over year, including a significant change in 2008. Patients who required pharmacy involvement were younger, sicker, and had longer intensive care unit, hospital, and ventilator duration. link2 Average central line infections and central line entry rates decreased significantly over the study period.

Increased pharmacist presence in the PICU is associated with increased interventions and prevention of adverse drug events. Pharmacist participation during rounds and order entry substantially improved the care of critically sick children and should be encouraged.
Increased pharmacist presence in the PICU is associated with increased interventions and prevention of adverse drug events. Pharmacist participation during rounds and order entry substantially improved the care of critically sick children and should be encouraged.Generalized convulsive status epilepticus (GCSE) is one of the most common neurologic emergencies and can be associated with significant morbidity and mortality if not treated promptly and aggressively. Management of GCSE is staged and generally involves the use of life support measures, identification and management of underlying causes, and rapid initiation of anticonvulsants. The purpose of this article is to review and evaluate published reports regarding the treatment of impending, established, refractory, and super-refractory GCSE in pediatric patients.Glycolate, malate, lactate, and 2-hydroxyglutarate are important 2-hydroxy acids (2HA) in plant metabolism. Most of them can be found as D- and L-stereoisomers. These 2HA play an integral role in plant primary metabolism, where they are involved in fundamental pathways such as photorespiration, tricarboxylic acid cycle, glyoxylate cycle, methylglyoxal pathway, and lysine catabolism. Recent molecular studies in Arabidopsis thaliana have helped elucidate the participation of these 2HA in in plant metabolism and physiology. In this chapter, we summarize the current knowledge about the metabolic pathways and cellular processes in which they are involved, focusing on the proteins that participate in their metabolism and cellular/intracellular transport in Arabidopsis.The [Formula see text] transition form factor is analyzed for the first time in both space- and time-like regions at low and intermediate energies in a model-independent approach through the use of rational approximants. The [Formula see text] experimental data provided by the A2 Collaboration in the very low-energy region of the dielectron invariant mass distribution allows for the extraction of the most precise up-to-date slope and curvature parameters of the form factors as well as their values at zero and infinity. The impact of these new results on the mixing parameters of the [Formula see text]-[Formula see text] system, together with the role played by renormalization dependent effects, and on the determination of the [Formula see text] couplings from [Formula see text] and [Formula see text] radiative decays is also discussed.A search for Higgs boson pair production [Formula see text] is performed with 19.5 fb[Formula see text] of proton-proton collision data at [Formula see text] TeV, which were recorded by the ATLAS detector at the Large Hadron Collider in 2012. The decay products of each Higgs boson are reconstructed as a high-momentum [Formula see text] system with either a pair of small-radius jets or a single large-radius jet, the latter exploiting jet substructure techniques and associated b-tagged track-jets. No evidence for resonant or non-resonant Higgs boson pair production is observed. The data are interpreted in the context of the Randall-Sundrum model with a warped extra dimension as well as the two-Higgs-doublet model. An upper limit on the cross-section for [Formula see text] of 3.2 (2.3) fb is set for a Kaluza-Klein graviton [Formula see text] mass of 1.0 (1.5) TeV, at the 95 % confidence level. The search for non-resonant Standard Model hh production sets an observed 95 % confidence level upper limit on the production cross-section [Formula see text] of 202 fb, compared to a Standard Model prediction of [Formula see text] fb.Various approaches have been used to select control groups in observational studies (1) from within the intervention area; (2) from a convenience sample, or randomly chosen areas; (3) from areas matched on area-level characteristics; and (4) nationally. The consequences of the decision are rarely assessed but, as we show, it can have complex impacts on confounding at both the area and individual levels. We began by reanalyzing data collected for an evaluation of a rapid response service on rates of unplanned hospital admission. Balance on observed individual-level variables was better with external than local controls, after matching. Further, when important prognostic variables were omitted from the matching algorithm, imbalances on those variables were also minimized using external controls. link3 Treatment effects varied markedly depending on the choice of control area, but in the case study the variation was minimal after adjusting for the characteristics of areas. We used simulations to assess relative bias and means-squared error, as this could not be done in the case study. A particular feature of the simulations was unexplained variation in the outcome between areas. We found that the likely impact of unexplained variation for hospital admissions dwarfed the benefits of better balance on individual-level variables, leading us to prefer local controls in this instance. In other scenarios, in which there was less unexplained variation in the outcome between areas, bias and mean-squared error were optimized using external controls. We identify some general considerations relevant to the choice of control population in observational studies.
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