Search

Purpose: Prior literature evaluating the importance of timely second-dose antibiotics in patients with sepsis has led to better outcomes and a possible reduction in mortality, length of mechanical ventilation, and length of time requiring vasopressors. Objective: To evaluate the impact of a newly developed pharmacist-led two-dose cefepime protocol implemented within an emergency department (ED) service. Methods: This was a retrospective, single-center, pre-post observational cohort study. Institutional review board approval was obtained. The primary endpoint was a reduction in time between the first and the second doses of antibiotics for patients with sepsis who present to the emergency department. Secondary endpoints included length of vasopressor therapy, intensive care unit (ICU) length of stay, hospital length of stay, duration of mechanical ventilation, and mortality. Results: A total of 84 patients were included in the pharmacist-led two-dose hospital protocol and 79 patients were included in the historical control. In the control cohort, the median time between the first and second dose of antibiotics was 12 hours vs 8.5 hours in the tested cohort. The average time requiring vasopressors was 1.20 days for the control cohort vs.46 days for the post-implementation group. Lastly, the median hospital length of stay in days was 8 for the control group vs 7 for the tested cohort. Conclusion: Implementation of a pharmacist-led two-dose cefepime protocol was associated with a numerically lower duration between second-dose antibiotics, days requiring vasopressors, and a slight reduction in hospital length of stay. [ABSTRACT FROM AUTHOR]

The use of the alkene-substituted cyclopentadienyl ligand, [(C5Me4)SiMe2(Ch2CH dbond CH2](super -), to probe metal-olefin versus metal-counteranion interactions in a cationic metallocene environment is reported. The tethred olefin can make it easier to access metallocenes and allow olefin complexes of lanthanides to be studied in solution and in the solid state.

For decades, the dental profession has provided the full spectrum of anesthesia services ranging from local anesthesia to general anesthesia in the office-based ambulatory environment to alleviate pain and anxiety. However, despite a reported record of safety, complications occasionally occur. Two common contributing factors to general anesthesia and sedation complications are medication errors and adverse drug events. The prevention and early detection of these complications should be of paramount importance to all dental providers who administer or otherwise use anesthesia services. Unfortunately, there is a lack of literature currently available regarding medication errors and adverse drug events involving anesthesia for dentistry. As a result, the profession is forced to look to the medical literature regarding these issues not only to assess the likely severity of the problem but also to develop preventive methods specific for general anesthesia and sedation as practiced within dentistry. Part 1 of this 2-part article illuminated the problems of medication errors and adverse drug events, primarily as documented within medicine. Part 2 will focus on how these complications affect dentistry, discuss several of the methods that medical anesthesia has implemented to manage such problems that may have utility in dentistry, and introduce a novel method for addressing these issues within dentistry known as the Dental Anesthesia Medication Safety Paradigm (DAMSP). [ABSTRACT FROM AUTHOR]

Study Objective: To compare analgesic efficacy and safety of intravenous lidocaine and ketorolac combination to each analgesic alone for ED patients with suspected renal colic.Methods: We conducted a randomized, double-blind trial comparing analgesic efficacy of a combination of intravenous lidocaine (1.5 mg/kg) and ketorolac (30 mg), to ketorolac (30 mg), and to lidocaine (1.5 mg/kg) in patients aged 18-64 presenting to the ED with suspected renal colic. Primary outcome included difference in pain scores between the groups at 30 min. Secondary outcomes included a comparative reduction in pain scores in each group from baseline to 30 and 60 min as well as rates of adverse events and need for rescue analgesia at 30 and 60 min.Results: We enrolled 150 subjects (50 per group). The difference in mean pain scores at 30 min between Lidocaine and Lidocaine/Ketorolac groups was -2.89 (95% CI: -4.39 to -1.39); between Ketorolac and Lidocaine/Ketorolac group was -0.92 (95% CI: -2.44 to 0.61); and between Ketorolac and Lidocaine was -1.98 (95% CI: -3.69 to -0.27). A comparative percentage of subjects in each group required rescue analgesia at 30 and 60 min. No clinically concerning changes in vital signs were observed. No serious adverse events occurred in either group. Commonly reported adverse effects were dizziness, nausea, and headache.Conclusion: The administration of intravenous lidocaine/ketorolac combination to ED patients with suspected renal colic results in better analgesia in comparison to lidocaine alone but provides no analgesic advantages over ketorolac alone. Clinicaltrials.gov Registration: NCT02902770. [ABSTRACT FROM AUTHOR]

The article focuses on vaccines as medicines that aid the immune system in fighting diseases, including common illnesses and cancer, by training the immune system to target harmful germs and cells.

For decades, the dental profession has provided anesthesia services in office-based, ambulatory settings to alleviate pain and anxiety, ranging from local anesthesia to general anesthesia. However, despite a reported record of safety, complications occasionally occur. Two common contributing factors to general anesthesia and sedation complications are medication errors and adverse drug events. The prevention and early detection of these complications should be of paramount importance to all dental providers who administer or otherwise use anesthesia services. Unfortunately, there is a substantial lack of literature currently available regarding medication errors and adverse drug events involving anesthesia for dentistry. As a result, the profession is forced to look to the medical literature regarding these issues not only to assess the likely severity of the problem but also to develop preventive methods specific for general anesthesia and sedation as practiced within dentistry. Part 1 of this 2-part article will illuminate the problems of medication errors and adverse drug events, primarily as documented within medicine. Part 2 will focus on how these complications affect dentistry, discuss several of the methods that medicine has implemented to manage such problems, and introduce a method for addressing these issues with the dental anesthesia medication safety paradigm. [ABSTRACT FROM AUTHOR]

Study Objective: We compare the analgesic efficacy and safety of subdissociative intravenous-dose ketamine (SDK) versus morphine in geriatric Emergency Department (ED) patients.Methods: This was a prospective, randomized, double-blind trial evaluating ED patients aged 65 and older experiencing moderate to severe acute abdominal, flank, musculoskeletal, or malignant pain. Patients were randomized to receive SDK at 0.3 mg/kg or morphine at 0.1 mg/kg by short intravenous infusion over 15 min. Evaluations occurred at 15, 30, 60, 90, and 120 min. Primary outcome was reduction in pain at 30 min. Secondary outcomes included overall rates of adverse effects and incidence of rescue analgesia.Results: Thirty patients per group were enrolled in the study. The primary change in mean pain scores was not significantly different in the ketamine and morphine groups: 9.0 versus 8.4 at baseline (mean difference 0.6; 95% CI -0.30 to 1.43) and 4.2 versus 4.4 at 30 min (mean difference -0.2; 95% CI -1.93 to1.46). Patients in the SDK group reported higher rates of psychoperceptual adverse effects at 15, 30, and 60 min post drug administration. Two patients in the ketamine group and one in the morphine group experienced brief desaturation episodes. There were no statistically significant differences with respect to changes in vital signs and need for rescue medication.Conclusion: SDK administered at 0.3 mg/kg over 15 min provides analgesic efficacy comparable to morphine for short-term treatment of acute pain in the geriatric ED patients but results in higher rates of psychoperceptual adverse effects. ClinicalTrials.gov Registration #: NCT02673372. [ABSTRACT FROM AUTHOR]

The utility of polydentate monoanionic [Zr(sub 2)(O(super i)Pr)(sub 9)] in generating arene-soluble, unsolvated, mixed-metal Zr/Ce and Zr/Y complexes is described. The synthesis of other mixed-metal zirconium lanthanide complexes is studied to explore the relationship of metal size to structure.

Study Objective: Compare adverse effects and analgesic efficacy of low-dose ketamine for acute pain in the ED administered either by single intravenous push (IVP) or short infusion (SI).Methods: Patients 18-65, presenting to ED with acute abdominal, flank, or musculoskeletal pain with initial pain score≥5, were randomized to ketamine 0.3mg/kg by either IVP or SI with placebo double-dummy. Adverse effects were evaluated by Side Effects Rating Scale for Dissociative Anesthetics (SERSDA) and Richmond Agitation-Sedation Scale (RASS) at 5, 15, 30, 60, 90, and 120min post-administration; analgesic efficacy was evaluated by Numerical Rating Scale (NRS).Results: 48 patients enrolled in the study. IVP group had higher overall rates of feeling of unreality on SERSDA scale: 92% versus 54% (difference 37.5%; p=0.008; 95% CI 9.3-59.5%). At 5min median severity of feeling of unreality was 3.0 for IVP versus 0.0 for SI (p=0.001). IVP also showed greater rates of sedation on RASS scale at 5min: median RASS -2.0 versus 0.0 (p=0.01). Decrease in mean pain scores from baseline to 15min was similar across groups: 5.2±3.53 (95% CI 3.7-6.7) for IVP; 5.75±3.48 (95% CI 4.3-7.2) for SI. There were no statistically significant differences with respect to changes in vital signs and need for rescue medication.Conclusion: Low-dose ketamine given as a short infusion is associated with significantly lower rates of feeling of unreality and sedation with no difference in analgesic efficacy in comparison to intravenous push. [ABSTRACT FROM AUTHOR]

The common γ chain family of cytokine receptors plays a plethora of roles during the early development, activation, and terminal differentiation of the lymphocyte lineages. The most recently identified member of this family, the IL-21R, is expressed to varying degrees on B, T lymphocytes, and natural killer (NK) cells, whereas IL-21, is reportedly only produced by activated CD4+T cells. In keeping with this expression pattern the IL-21:IL-21R interaction is important for the latter stages and function of all three lymphoid lineages. IL-21 is a regulator of B-cell differentiation to plasma cells as well as immunoglobulin class switching. In contrast, within the T-cell lineage, IL-21 acts as a co-stimulator of proliferation, enhances memory response, and modulates homeostasis. Within the innate immune system IL-21 has a role in the terminal differentiation of NK cells, enhancing cytotoxic function while also decreasing cellular viability. These immune maturation and stimulating functions have resulted in IL-21 being tested in a variety of models of immunity. In these contexts, IL-21 has shown very promising efficacy in a number of antitumor immune responses mediated by NK and or T lymphocytes. [ABSTRACT FROM AUTHOR]

Describes the coordination chemistry of the 2,3-dimethylindolide ligand with potassium, yttrium and samarium. Examination of the alternatives of cyclopentadienyl groups; Presence of arene ring on each side of pyrrole; Effects of the changing substitution on cyclopentadienyl ligands.

THF-solvated KC5Me5 and KC5Me4SiMe2CH2CH&z.dbnd6;CH2 complexes crystallize with extended structures that provide information on bent metallocenes containing potassium, [(μ-C5R5)K(μ-C5R5)]−. The substructures of [(THF)K(μ-C5Me5)]n, [(THF)2K(μ-C5Me5)]n, and [(THF)K(μ-C5Me4SiMe2CH2CH&z.dbnd6;CH2)]n display (μ-C5R5)K(μ-C5R5) angles of 137.9–143.7°. The olefin substituent in [(THF)K(μ-C5Me4SiMe2CH2CH&z.dbnd6;CH2)]n approaches potassium with K⋯C distances of 3.58 and 4.20 A˚. [Copyright &y& Elsevier]

Background: Ibuprofen (Motrin; Johnson & Johnson) and acetaminophen (APAP, paracetamol) are the most commonly used analgesics in the pediatric emergency department (ED) for managing a variety of acute traumatic and nontraumatic painful conditions. The multimodal pain management of using a combination of ibuprofen plus acetaminophen has the potential to result in greater analgesia.Objective: We compared the analgesic efficacy of a combination of oral ibuprofen plus acetaminophen with either analgesic alone for pediatric ED patients with acute pain.Methods: We performed a randomized, double-blind superiority trial assessing and comparing the analgesic efficacy of a combination of oral ibuprofen (10 mg/kg dose) plus acetaminophen (15 mg/kg per dose) to either analgesic alone for the treatment of acute traumatic and nontraumatic pain in the pediatric ED. Primary outcomes included a difference in pain scores among the three groups at 60 min.Results: We enrolled 90 patients (30 per group). The difference in mean pain scores at 60 min between acetaminophen and combination groups was 0.30 (95% confidence interval [CI] -0.84 to 1.83); between ibuprofen and combination groups was -0.33 (95% CI -1.47 to 0.80); and between acetaminophen and ibuprofen groups was 0.63 (95% CI -0.54 to 1.81). Reductions in pain scores from baseline to 60 min were similar for all patients in each of the three groups. No adverse events occurred in any group.Conclusions: We found similar analgesic efficacy of oral ibuprofen and acetaminophen in comparison with each analgesic alone for short-term treatment of acute pain in the pediatric ED, but the trial was underpowered to demonstrate the analgesic superiority of the combination of oral ibuprofen plus acetaminophen in comparison with each analgesic alone. [ABSTRACT FROM AUTHOR]

Study Objective: Nonsteroidal anti-inflammatory drugs (NSAIDs) are used extensively for the management of acute pain, with ibuprofen being one of the most frequently used oral analgesics in the emergency department (ED). We compare the analgesic efficacy of oral ibuprofen at 3 different doses for adult ED patients with acute pain., Methods: This was a randomized, double-blind trial comparing analgesic efficacy of 3 doses of oral ibuprofen (400, 600, and 800 mg) in adult ED patients with acute painful conditions. Primary outcome included difference in pain scores between the 3 groups at 60 minutes., Results: We enrolled 225 subjects (75 per group). The difference in mean pain scores at 60 minutes between the 400- and 600-mg groups was -0.14 (95% confidence interval [CI] -0.67 to 0.39); between the 400- and 800-mg groups, 0.14 (95% CI -0.65 to 0.37); and between the 600- and 800-mg groups, 0.00 (95% CI -0.47 to 0.47). Reductions in pain scores from baseline to 60 minutes were similar for all subjects in each of the 3 groups. No adverse events occurred in any group., Conclusion: Oral ibuprofen administered at doses of 400, 600, and 800 mg has similar analgesic efficacy for short-term pain relief in adult patients presenting to the ED with acute pain., (Copyright © 2019 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Although NK cells are well known for their cytotoxic functions, they also produce an array of immunoregulatory cytokines and chemokines. During an immune response, NK cells are exposed to complex combinations of cytokines that influence their differentiation and function. In this study, we have examined the phenotypic and functional consequences of exposing mouse NK cells to IL-4, IL-12, IL-15, IL-18, and IL-21 and found that although all factors induced signs of maturation, characterized by decreased proliferation and IFN-γ secretion, distinct combinations induced unique cytokine secretion profiles. In contrast, the immunosuppressive factors IL-10 and TGF-β had little direct effect on NK cell effector functions. Sustained IL-18 signals resulted in IL-13 and GM-CSF production, whereas IL-12 and IL-21 induced IL-10 and TNF-α. Surprisingly, with the exception of IL-21, all cytokines suppressed cytotoxic function of NK cells at the expense of endogenous cytokine production suggesting that "helper-type" NK cells were generated. The cytokine signals also profoundly altered the cell surface phenotype of the NK cells-a striking example being the downregulation of the activating receptor NKG2D by IL-4 that resulted in decreased NKG2D-dependent killing. IL-4 exposure also modulated NKG2D expression in vivo suggesting it is functionally important during immune responses. This study highlights the plasticity of NK cell differentiation and suggests that the relative abundance of cytokines at sites of inflammation will lead to diverse outcomes in terms of NK cell phenotype and interaction with the immune system.

Interferon-producing killer dendritic cells (IKDCs) have been described as possessing the lytic potential of NK cells and the antigen-presenting capacity of dendritic cells (DCs). In this study, we examine the lytic function and antigen-presenting capacity of mouse spleen IKDCs, including those found in DC preparations. IKDCs efficiently killed NK cell targets, without requiring additional activation stimuli. However, in our hands, when exposed to protein antigen or to MHC class II peptide, IKDCs induced little or no T cell proliferation relative to conventional DCs or plasmacytoid DCs, either before or after activation with CpG, or in several disease models. Certain developmental features indicated that IKDCs resembled NK cells more than DCs. IKDCs, like NK cells, did not express the transcription factor PU.1 and were absent from recombinase activating gene-2-null, common gamma-chain-null (Rag2(-/-)Il2rg(-/-)) mice. When cultured with IL-15 and -18, IKDCs proliferated extensively, like NK cells. Under these conditions, a proportion of expanded IKDCs and NK cells expressed high levels of surface MHC class II. However, even such MHC class II(+) IKDCs and NK cells induced poor T cell proliferative responses compared with DCs. Thus, IKDCs resemble NK cells functionally, and neither cell type could be induced to be effective antigen-presenting cells.

NK cells are important for the clearance of tumors, parasites, and virus-infected cells. Thus, factors that control NK cell numbers and function are critical for the innate immune response. A subset of NK cells express the inhibitory killer cell lectin-like receptor G1 (KLRG1). In this study, we identify that KLRG1 expression is acquired during periods of NK cell division such as development and homeostatic proliferation. KLRG1(+) NK cells are mature in phenotype, and we show for the first time that these cells have a slower in vivo turnover rate, reduced proliferative response to IL-15, and poorer homeostatic expansion potential compared with mature NK cells lacking KLRG1. Transfer into lymphopenic recipients indicate that KLRG1(-) NK cells are precursors of KLRG1(+) NK cells and KLRG1 expression accumulates following cell division. Furthermore, KLRG1(+) NK cells represent a significantly greater proportion of NK cells in mice with enhanced NK cell numbers such as Cd45(-/-) mice. These data indicate that NK cells acquire KLRG1 on their surface during development, and this expression correlates with functional distinctions from other peripheral NK cells in vivo.

Background: Natural killer (NK) cells have emerged as major players in anti-viral and anti-tumour immune responses. Like cytotoxic T lymphocytes (CTL), they express perforin and are potent secretors of gamma-interferon (IFN-gamma). However, there is conflicting evidence about their role in mediating rejection of xenogeneic tissue., Methods: A pig-to-mouse peritoneal cell model of xenotransplantation was used to investigate the effect of NK deficiency on xenograft recovery and the possible mechanisms behind this NK-mediated graft rejection. gamma c(-/-)RAG(-/-) mice were used as a model of NK deficiency. Additionally, NK cells were depleted in RAG(-/-) mice using anti-asialo GM1. The contributions of IFN-gamma, perforin and NKT cells were studied using knock-out mice that were depleted in vivo of T cells. Mice were injected with 10(7) pig cells intraperitoneally and peritoneal fluid was assessed 5 days later for xenograft recovery and phenotypic analysis. The requirement for NK cells for xenograft rejection was also assessed using luciferase-transfected porcine cells in a renal subcapsular model of transplantation., Results: Pig cell recovery was enhanced in both gamma c(-/-)RAG(-/-) and NK-depleted RAG(-/-) mice when compared with RAG(-/-) control mice. IFN-gamma(-/-) mice depleted of T cells also demonstrated superior graft survival compared with their B6 counterparts. However, there were minimal graft survival differences between Pfp(-/-) and B6 control mice. Similarly, a deficiency in NKT cells did not improve pig xenograft recovery from the peritoneum of these mice., Conclusions: Therefore, we conclude that NK cells, but not NKT cells, are important mediators of xenograft rejection in the peritoneal cavity, and that their role may be unmasked in the absence of T cells. The mechanism for this xenorejection appears to involve IFN-gamma but is perforin independent.

IL-21 is a recently identified cytokine that stimulates mouse NK cell effector functions in vitro. In this study we demonstrate that IL-21 achieves its stimulatory effect by inducing the development of mature NK cells into a large granular lymphocyte phenotype with heightened effector function. IL-21 treatment results in increased cell size and granularity and a corresponding decrease in cell viability and proliferative potential. These cells up-regulate the expression of the inhibitory CD94-NKG2A receptor complex and the activation markers CD154 and killer cell, lectin-like-receptor G1. Surprisingly, IL-21 treatment also results in down-regulation of the pan-NK marker, NK1.1. Coinciding with these cellular changes IL-21 enhances cytolytic capacity across a spectrum of target sensitivities and induces IL-10 and IFN-gamma production. In vivo treatment with IL-21 results in a very similar activation and phenotypic maturation of NK cells as well as a potent increase in NK cell-mediated anti-tumor immunity that is perforin dependent. These developmental changes suggested that IL-21 functions to induce the terminal differentiation of mouse NK cells, resulting in heightened NK cell-mediated cytotoxicity and immune surveillance.