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  • Article
    Norris M, Mak H, Fong CT, Walters AM, Hoang CV, Lele AV.
    Cureus. 2024 Jun;16(6):e61952.
    Objective There is growing interest in the use of phenobarbital for alcohol withdrawal syndrome in critically ill patients, though experience in neurologically injured patients is limited. The purpose of this study was to compare the safety and effectiveness of phenobarbital-containing alcohol withdrawal regimens versus benzodiazepine monotherapy in the neurocritical care unit. Methods We conducted a retrospective cohort study of adult patients admitted to the neurocritical care unit from January 2014 through November 2021 who received pharmacologic treatment for alcohol withdrawal. Treatment groups were defined as benzodiazepine monotherapy versus phenobarbital alone or in combination with benzodiazepines. The primary outcome was the percentage of patients requiring intubation after receiving alcohol withdrawal treatment. Secondary outcomes included all-cause, in-hospital mortality, intensive care unit length of stay, discharge disposition, change in Glasgow Coma Scale (GCS) score, and the use of adjunctive agents. Results We analyzed data from 156 patients, with 77 (49%) in the benzodiazepine group and 79 (51%) in the phenobarbital combination group. The groups were well-balanced for baseline characteristics, though more males (67, 85%) were in the phenobarbital group. Only three (1.9%) patients received phenobarbital monotherapy, and the rest (153, 98.1%) received combination therapy. The percentage of patients requiring mechanical ventilation was significantly higher in the phenobarbital combination group compared to benzodiazepine monotherapy (39% (n=31) versus 13% (n=10); OR: 4.33, 95% CI: 1.94-9.66; p<0.001). The use of adjunctive propofol and dexmedetomidine was higher in the phenobarbital group (propofol 35% (n= 28) versus 9% (n=7) and dexmedetomidine 30% (n=24) versus 5% (n=4), respectively). Patients in the phenobarbital group also had lower GCS scores and higher Clinical Institute Withdrawal Assessment of Alcohol (CIWA-Ar) scores during their intensive care unit admission, possibly suggesting more severe alcohol withdrawal. There was no difference in intensive care unit length of stay, all-cause, in-hospital mortality, discharge disposition, or therapeutic adjuncts. Conclusions Combination therapy of phenobarbital plus benzodiazepines was associated with higher odds of requiring mechanical ventilation. Few patients received phenobarbital monotherapy. Additional studies are needed to better compare the effects of phenobarbital monotherapy versus benzodiazepines in neurocritical patients.
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  • Article
    Jensen L, Farook MF, Reiter LT.
    PLoS One. 2013;8(4):e61952.
    The molecular defects associated with Angelman syndrome (AS) and 15q duplication autism are directly correlated to expression levels of the E3 ubiquitin ligase protein UBE3A. Here we used Drosophila melanogaster to screen for the targets of this ubiquitin ligase under conditions of both decreased (as in AS) or increased (as in dup(15)) levels of the fly Dube3a or human UBE3A proteins. Using liquid phase isoelectric focusing of proteins from whole fly head extracts we identified a total of 50 proteins that show changes in protein, and in some cases transcriptional levels, when Dube3a fluctuates. We analyzed head extracts from cytoplasmic, nuclear and membrane fractions for Dube3a regulated proteins. Our results indicate that Dube3a is involved in the regulation of cellular functions related to ATP synthesis/metabolism, actin cytoskeletal integrity, both catabolism and carbohydrate metabolism as well as nervous system development and function. Sixty-two percent of the proteins were >50% identical to homologous human proteins and 8 have previously be shown to be ubiquitinated in the fly nervous system. Eight proteins may be regulated by Dube3a at the transcript level through the transcriptional co-activation function of Dube3a. We investigated one autism-associated protein, ATPα, and found that it can be ubiquitinated in a Dube3a dependent manner. We also found that Dube3a mutants have significantly less filamentous actin than wild type larvae consistent with the identification of actin targets regulated by Dube3a. The identification of UBE3A targets is the first step in unraveling the molecular etiology of AS and duplication 15q autism.
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  • Book
    Frederick L. Kiechle, editor ; Dorothy M. Adcock, Samuel I. McCash, Deborah Sesok-Pizzini, co-editors
    Contents:
    Why is collecting a blood sample important?
    You and your patient
    How do you protect your patient and yourself using standard precautions?
    Sterility
    Disposal of used materials
    What is blood?
    Recommended volume limits for a single blood draw
    How is blood collected?
    Blood collection equipment
    The phlebotomy area
    The test requisition
    Representative blood collection tubes
    Timed specimens
    Approaching the patient
    The venipuncture from an arm vein
    Recommended order of draw for multiple specimen collection
    The difficult venipuncture
    Intravenous fluids and the venipuncture
    Collection of venous blood gases
    Identification and labeling of the blood specimen tube
    The difficult patient
    The missing patient
    The patient has a reaction
    The skin puncture
    Obtaining blood from babies
    The blood smear
    The blood culture
    Collecting blood specimens under special circumstances
    Your safety
    Competency assessment
    Your attitude
    Appendix 1: Drawing blood from existing intravascular devices
    Appendix 2: Intraosseous cannulation used for blood analysis and infusion
    Appendix 3: Aids for visualizing veins under the skin
    Appendix 4: Ultrasound-guided peripheral intravenous cannulation
    Appendix 5: Quality assurance
    Appendix 6: Additional resources.