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Results: 1 to 10 of 27

Publication Record


Intensive Care Unit Delirium and Intensive Care Unit-Related Posttraumatic Stress Disorder.
Marra A, Pandharipande PP, Patel MB
(2017) Surg Clin North Am 97: 1215-1235
MeSH Terms: Antipsychotic Agents, Brain Diseases, Cognition Disorders, Conscious Sedation, Critical Care, Critical Illness, Delirium, Early Ambulation, Exercise Therapy, Family, Humans, Pain Measurement, Stress Disorders, Post-Traumatic, Ventilator Weaning
Show Abstract · Added June 26, 2018
Delirium is one of the most common behavioral manifestations of acute brain dysfunction in the intensive care unit (ICU) and is a strong predictor of worse outcome. Routine monitoring for delirium is recommended for all ICU patients using validated tools. In delirious patients, a search for all reversible precipitants is the first line of action and pharmacologic treatment should be considered when all causes have been ruled out, and it is not contraindicated. Long-term morbidity has significant consequences for survivors of critical illness and for their caregivers. ICU patients may develop posttraumatic stress disorder related to their critical illness experience.
Published by Elsevier Inc.
0 Communities
1 Members
0 Resources
MeSH Terms
Defining a Novel Role for the Pdx1 Transcription Factor in Islet β-Cell Maturation and Proliferation During Weaning.
Spaeth JM, Gupte M, Perelis M, Yang YP, Cyphert H, Guo S, Liu JH, Guo M, Bass J, Magnuson MA, Wright C, Stein R
(2017) Diabetes 66: 2830-2839
MeSH Terms: Animals, Cell Proliferation, Gene Expression Regulation, Homeodomain Proteins, Insulin-Secreting Cells, Male, Mice, Mice, Knockout, Oxidative Phosphorylation, Trans-Activators, Weaning
Show Abstract · Added August 1, 2017
The transcription factor encoded by the gene is a critical transcriptional regulator, as it has fundamental actions in the formation of all pancreatic cell types, islet β-cell development, and adult islet β-cell function. Transgenic- and cell line-based experiments have identified 5'-flanking conserved sequences that control pancreatic and β-cell type-specific transcription, which are found within areas I (bp -2694 to -2561), II (bp -2139 to -1958), III (bp -1879 to -1799), and IV (bp -6200 to -5670). Because of the presence in area IV of binding sites for transcription factors associated with pancreas development and islet cell function, we analyzed how an endogenous deletion mutant affected expression embryonically and postnatally. The most striking result was observed in male mutant mice after 3 weeks of birth (i.e., the onset of weaning), with only a small effect on pancreas organogenesis and no deficiencies in their female counterparts. Compromised Pdx1 mRNA and protein levels in weaned male mutant β-cells were tightly linked with hyperglycemia, decreased β-cell proliferation, reduced β-cell area, and altered expression of Pdx1-bound genes that are important in β-cell replication, endoplasmic reticulum function, and mitochondrial activity. We discuss the impact of these novel findings to gene regulation and islet β-cell maturation postnatally.
© 2017 by the American Diabetes Association.
2 Communities
2 Members
0 Resources
11 MeSH Terms
Threshold-Dependent Cooperativity of Pdx1 and Oc1 in Pancreatic Progenitors Establishes Competency for Endocrine Differentiation and β-Cell Function.
Henley KD, Stanescu DE, Kropp PA, Wright CVE, Won KJ, Stoffers DA, Gannon M
(2016) Cell Rep 15: 2637-2650
MeSH Terms: Animals, Basic Helix-Loop-Helix Transcription Factors, Cell Count, Cell Differentiation, Embryo, Mammalian, Gene Dosage, Gene Expression Regulation, Developmental, Gene Ontology, Gene Regulatory Networks, Glucose, Hepatocyte Nuclear Factor 6, Heterozygote, Homeodomain Proteins, Homeostasis, Insulin-Secreting Cells, Mice, Multigene Family, Nerve Tissue Proteins, Stem Cells, Trans-Activators, Weaning
Show Abstract · Added July 5, 2016
Pdx1 and Oc1 are co-expressed in multipotent pancreatic progenitors and regulate the pro-endocrine gene Neurog3. Their expression diverges in later organogenesis, with Oc1 absent from hormone+ cells and Pdx1 maintained in mature β cells. In a classical genetic test for cooperative functional interactions, we derived mice with combined Pdx1 and Oc1 heterozygosity. Endocrine development in double-heterozygous pancreata was normal at embryonic day (E)13.5, but defects in specification and differentiation were apparent at E15.5, the height of the second wave of differentiation. Pancreata from double heterozygotes showed alterations in the expression of genes crucial for β-cell development and function, decreased numbers and altered allocation of Neurog3-expressing endocrine progenitors, and defective endocrine differentiation. Defects in islet gene expression and β-cell function persisted in double heterozygous neonates. These results suggest that Oc1 and Pdx1 cooperate prior to their divergence, in pancreatic progenitors, to allow for proper differentiation and functional maturation of β cells.
Published by Elsevier Inc.
1 Communities
2 Members
0 Resources
21 MeSH Terms
Pharmacist leadership in ICU quality improvement: coordinating spontaneous awakening and breathing trials.
Stollings JL, Foss JJ, Ely EW, Ambrose AM, Rice TW, Girard TD, Wheeler AP
(2015) Ann Pharmacother 49: 883-91
MeSH Terms: Critical Care, Humans, Intensive Care Units, Leadership, Pharmacists, Pharmacy Service, Hospital, Prospective Studies, Quality Improvement, Respiration, Artificial, Ventilator Weaning
Show Abstract · Added September 23, 2015
BACKGROUND - Coordinating efforts across disciplines in the intensive care unit is a key component of quality improvement (QI) efforts. Spontaneous awakening trials (SATs) and spontaneous breathing trials (SBTs) are considered key components of guidelines, yet unfortunately are often not done or coordinated properly.
OBJECTIVE - To determine if a pharmacist-driven awakening and breathing coordination (ABC) QI program would improve compliance (ie, process measures) as compared with the previous protocol, which did not involve pharmacists.
METHODS - The QI program included pharmacist-led education, daily discussion on rounds, and weekly performance reports to staff. Using a pre-QI versus during-QI versus post-QI intervention design, we compared data from 500 control ventilator-days (pre-QI period) versus 580 prospective ventilator-days (during-QI period). We then evaluated the sustainability of the QI program in 216 ventilator-days in the post-QI period.
RESULTS - SAT safety screens were performed on only 20% pre-QI patient-days versus 97% of during-QI patient-days (P < 0.001) and 100% of post-QI patient-days (P = 0.25). The rates of passing the SAT safety screen in pre-QI and during-QI periods were 63% versus 78% (P = 0.03) and 81% in the post-QI period (P = 0.86). The rates of SATs among eligible patients on continuous infusions were only 53% in the pre-QI versus 85% in the during-QI (P = 0.0001) and 87% in the post-QI (P = 1) periods.
CONCLUSIONS - In this QI initiative, a pharmacist-driven, interdisciplinary ABC protocol significantly improved process measures compliance, comparing the pre-QI versus during-QI rates of screening, performing, and coordinating SAT and SBTs, and these results were sustained in the 8-month follow-up period post-QI program.
© The Author(s) 2015.
0 Communities
1 Members
0 Resources
10 MeSH Terms
Selenoprotein P is the major selenium transport protein in mouse milk.
Hill KE, Motley AK, Winfrey VP, Burk RF
(2014) PLoS One 9: e103486
MeSH Terms: Animals, Animals, Newborn, Biological Transport, Electrophoresis, Polyacrylamide Gel, Female, Glutathione Peroxidase, In Situ Hybridization, Male, Mammary Glands, Animal, Mice, Inbred C57BL, Mice, Knockout, Milk, Selenium, Selenoprotein P, Weaning, Weight Gain
Show Abstract · Added September 28, 2015
Selenium is transferred from the mouse dam to its neonate via milk. Milk contains selenium in selenoprotein form as selenoprotein P (Sepp1) and glutathione peroxidase-3 (Gpx3) as well as in non-specific protein form as selenomethionine. Selenium is also present in milk in uncharacterized small-molecule form. We eliminated selenomethionine from the mice in these experiments by feeding a diet that contained sodium selenite as the source of selenium. Selenium-replete dams with deletion of Sepp1 or Gpx3 were studied to assess the effects of these genes on selenium transfer to the neonate. Sepp1 knockout caused a drop in milk selenium to 27% of the value in wild-type milk and a drop in selenium acquisition by the neonates to 35%. In addition to decreasing milk selenium by eliminating Sepp1, deletion of Sepp1 causes a decline in whole-body selenium, which likely also contributes to the decreased transfer of selenium to the neonate. Deletion of Gpx3 did not decrease milk selenium content or neonate selenium acquisition by measurable amounts. Thus, when the dam is fed selenium-adequate diet (0.25 mg selenium/kg diet), milk Sepp1 transfers a large amount of selenium to neonates but the transfer of selenium by Gpx3 is below detection by our methods.
0 Communities
1 Members
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16 MeSH Terms
Diurnal sedative changes during intensive care: impact on liberation from mechanical ventilation and delirium.
Seymour CW, Pandharipande PP, Koestner T, Hudson LD, Thompson JL, Shintani AK, Ely EW, Girard TD
(2012) Crit Care Med 40: 2788-96
MeSH Terms: Aged, Benzodiazepines, Circadian Rhythm, Clinical Protocols, Coma, Critical Care, Delirium, Dose-Response Relationship, Drug, Drug Therapy, Combination, Female, Humans, Hypnotics and Sedatives, Male, Middle Aged, Propofol, Prospective Studies, Respiration, Artificial, Ventilator Weaning
Show Abstract · Added September 23, 2015
OBJECTIVE - To determine whether benzodiazepine and propofol doses are increased at night and whether daytime and nighttime sedative doses are associated with delirium, coma, and delayed liberation from mechanical ventilation.
DESIGN - Single-center, prospective cohort study nested within the Awakening and Breathing Controlled randomized trial.
SETTING - Saint Thomas Hospital in Nashville, TN, from 2004 to 2006.
PATIENTS - Adult patients receiving mechanical ventilation for >12 hrs with continuous recording of hourly sedation dosing.
INTERVENTIONS - We measured hourly doses of benzodiazepine and propofol exposure during the daytime (7 AM to 11 PM) and nighttime (11 PM to 7 AM) for 5 days. We quantified nighttime dose increases by subtracting the average hourly daytime dose on the preceding day from subsequent average hourly nighttime dose. We used multivariable logistic regression to determine whether daytime and nighttime dose increases were independently associated with delirium, coma, and delayed liberation from mechanical ventilation.
MEASUREMENTS AND MAIN RESULTS - Among 140 patients, the median Acute Physiology and Chronic Health Evaluation II score was 27 (interquartile range 22-33). Among those receiving the sedatives, benzodiazepine and propofol doses were increased at night on 40% and 41% of patient-days, respectively. Of 485 patient-days, delirium was present on 160 (33%) and coma on 206 (42%). In adjusted models, greater daytime benzodiazepine dose was independently associated with failed spontaneous breathing trial and extubation, and subsequent delirium (p<.02 for all). Nighttime increase in benzodiazepine dose was associated with failed spontaneous breathing trial (p<.01) and delirium (p=.05). Daytime propofol dose was marginally associated with subsequent delirium (p=.06).
CONCLUSIONS - Nearly half of mechanically ventilated intensive care unit patients received greater doses of sedation at night, a practice associated with failed spontaneous breathing trials, coma, and delirium. Over the first 5 days in our study, patients spent 75% of their time in coma or delirium, outcomes that may be reduced by efforts to decrease sedative exposure during both daytime and nighttime hours in the intensive care unit.
0 Communities
1 Members
0 Resources
18 MeSH Terms
Enteral omega-3 fatty acid, gamma-linolenic acid, and antioxidant supplementation in acute lung injury.
Rice TW, Wheeler AP, Thompson BT, deBoisblanc BP, Steingrub J, Rock P, NIH NHLBI Acute Respiratory Distress Syndrome Network of Investigators, NHLBI ARDS Clinical Trials Network
(2011) JAMA 306: 1574-81
MeSH Terms: Acute Lung Injury, Adult, Aged, Antioxidants, Biomarkers, Dietary Supplements, Docosahexaenoic Acids, Double-Blind Method, Drug Therapy, Combination, Eicosapentaenoic Acid, Enteral Nutrition, Female, Humans, Inflammation, Intensive Care Units, Male, Middle Aged, Pneumonia, Sepsis, Survival Analysis, Treatment Outcome, Ventilator Weaning, gamma-Linolenic Acid
Show Abstract · Added March 5, 2014
CONTEXT - The omega-3 (n-3) fatty acids docosahexaenoic acid and eicosapentaenoic acid, along with γ-linolenic acid and antioxidants, may modulate systemic inflammatory response and improve oxygenation and outcomes in patients with acute lung injury.
OBJECTIVE - To determine if dietary supplementation of these substances to patients with acute lung injury would increase ventilator-free days to study day 28.
DESIGN, SETTING, AND PARTICIPANTS - The OMEGA study, a randomized, double-blind, placebo-controlled, multicenter trial conducted from January 2, 2008, through February 21, 2009. Participants were 272 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition at 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. All participants had complete follow-up.
INTERVENTIONS - Twice-daily enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants compared with an isocaloric control. Enteral nutrition, directed by a protocol, was delivered separately from the study supplement.
MAIN OUTCOME MEASURE - Ventilator-free days to study day 28.
RESULTS - The study was stopped early for futility after 143 and 129 patients were enrolled in the n-3 and control groups. Despite an 8-fold increase in plasma eicosapentaenoic acid levels, patients receiving the n-3 supplement had fewer ventilator-free days (14.0 vs 17.2; P = .02) (difference, -3.2 [95% CI, -5.8 to -0.7]) and intensive care unit-free days (14.0 vs 16.7; P = .04). Patients in the n-3 group also had fewer nonpulmonary organ failure-free days (12.3 vs 15.5; P = .02). Sixty-day hospital mortality was 26.6% in the n-3 group vs 16.3% in the control group (P = .054), and adjusted 60-day mortality was 25.1% and 17.6% in the n-3 and control groups, respectively (P = .11). Use of the n-3 supplement resulted in more days with diarrhea (29% vs 21%; P = .001).
CONCLUSIONS - Twice-daily enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants did not improve the primary end point of ventilator-free days or other clinical outcomes in patients with acute lung injury and may be harmful.
TRIAL REGISTRATION - clinicaltrials.gov Identifier: NCT00609180.
0 Communities
1 Members
0 Resources
23 MeSH Terms
Long-term cognitive and psychological outcomes in the awakening and breathing controlled trial.
Jackson JC, Girard TD, Gordon SM, Thompson JL, Shintani AK, Thomason JW, Pun BT, Canonico AE, Dunn JG, Bernard GR, Dittus RS, Ely EW
(2010) Am J Respir Crit Care Med 182: 183-91
MeSH Terms: Aged, Clinical Protocols, Cognition Disorders, Conscious Sedation, Critical Care, Depression, Female, Follow-Up Studies, Humans, Intensive Care Units, Male, Middle Aged, Neuropsychological Tests, Patient Discharge, Quality of Life, Respiration, Artificial, Stress Disorders, Post-Traumatic, Ventilator Weaning
Show Abstract · Added March 5, 2014
RATIONALE - Studies have shown that reducing sedation of critically ill patients shortens time on the ventilator and in the intensive care unit (ICU). Little is known, however, of how such strategies affect long-term cognitive, psychological, and functional outcomes.
OBJECTIVES - To determine the long-term effects of a wake up and breathe protocol that interrupts and reduces sedative exposure in the ICU.
METHODS - In this a priori planned substudy conducted at one tertiary care hospital during the Awakening and Breathing Controlled Trial, a multicenter randomized controlled trial, we assessed cognitive, psychological, and functional/quality-of-life outcomes 3 and 12 months postdischarge among 180 medical ICU patients randomized to paired daily spontaneous awakening trials with spontaneous breathing trials (SBTs) or to sedation per usual care plus daily SBTs.
MEASUREMENTS AND MAIN RESULTS - Cognitive impairment was less common in the intervention group at 3-month follow-up (absolute risk reduction, 20.2%; 95% confidence interval, 1.5-36.1%; P = 0.03) but not at 12-month follow-up (absolute risk reduction, -1.9%; 95% CI, -21.3 to 27.1%; P = 0.89). Composite cognitive scores, alternatively, were similar in the two groups at 3-month and 12-month follow-up (P = 0.80 and 0.61, respectively), as were symptoms of depression (P = 0.59 and 0.82) and posttraumatic stress disorder (P = 0.59 and 0.97). Activities of daily living, functional status, and mental and physical quality of life were similar between groups throughout follow-up.
CONCLUSIONS - In this trial, management of mechanically ventilated medical ICU patients with a wake up and breathe protocol resulted in similar cognitive, psychological, and functional outcomes among patients tested 3 and 12 months post-ICU. The proven benefits of this protocol, including improved 1-year survival, were not offset by adverse long-term outcomes. Clinical trial registered with www.clinicaltrials.gov (NCT 00097630).
0 Communities
3 Members
0 Resources
18 MeSH Terms
Sedation and weaning from mechanical ventilation: linking spontaneous awakening trials and spontaneous breathing trials to improve patient outcomes.
Hooper MH, Girard TD
(2009) Crit Care Clin 25: 515-25, viii
MeSH Terms: Analgesics, Conscious Sedation, Critical Care, Humans, Hypnotics and Sedatives, Outcome and Process Assessment, Health Care, Respiration, Treatment Outcome, Ventilator Weaning
Show Abstract · Added September 23, 2015
Liberation from mechanical ventilation is a vital treatment goal in the management of critically ill patients. The duration of mechanical ventilation is affected by strategies for ventilator weaning and sedation. The authors review literature on weaning from mechanical ventilation and delivery of sedation in critically ill patients, including current guidelines recommending the use of spontaneous breathing trials and spontaneous awakening trials. Implementation of these strategies in a wake-up-and-breathe protocol has demonstrated benefit over the use of spontaneous breathing trials alone.
0 Communities
1 Members
0 Resources
9 MeSH Terms
Donor postextubation hypotension and age correlate with outcome after donation after cardiac death transplantation.
Ho KJ, Owens CD, Johnson SR, Khwaja K, Curry MP, Pavlakis M, Mandelbrot D, Pomposelli JJ, Shah SA, Saidi RF, Ko DS, Malek S, Belcher J, Hull D, Tullius SG, Freeman RB, Pomfret EA, Whiting JF, Hanto DW, Karp SJ
(2008) Transplantation 85: 1588-94
MeSH Terms: Adult, Age Factors, Blood Pressure, Death, Female, Follow-Up Studies, Humans, Hypotension, Incidence, Intubation, Intratracheal, Kidney Transplantation, Liver Transplantation, Male, Middle Aged, Prognosis, Retrospective Studies, Risk Factors, Survival Rate, Tissue Donors, Tissue and Organ Procurement, United States, Ventilator Weaning
Show Abstract · Added May 22, 2014
BACKGROUND - Compared with standard donors, kidneys recovered from donors after cardiac death (DCD) exhibit higher rates of delayed graft function (DGF), and DCD livers demonstrate higher rates of biliary ischemia, graft loss, and worse patient survival. Current practice limits the use of these organs based on time from donor extubation to asystole, but data to support this is incomplete. We hypothesized that donor postextubation parameters, including duration and severity of hemodynamic instability or hypoxia might be a better predictor of subsequent graft function.
METHODS - We performed a retrospective examination of the New England Organ Bank DCD database, concentrating on donor factors including vital signs after withdrawal of support.
RESULTS - Prolonged, severe hypotension in the postextubation period was a better predictor of subsequent organ function that time from extubation to asystole. For DCD kidneys, this manifested as a trend toward increased DGF. For DCD livers, this manifested as increased rates of poor outcomes. Maximizing the predictive value of this test in the liver cohort suggested that greater than 15 min between the time when the donor systolic blood pressure drops below 50 mm Hg and flush correlates with increased rates of diffuse biliary ischemia, graft loss, or death. Donor age also correlated with worse outcome.
CONCLUSIONS - Time between profound instability and cold perfusion is a better predictor of outcome than time from extubation to asystole. If validated, this information could be used to predict DGF after DCD renal transplant and improve outcomes after DCD liver transplant.
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22 MeSH Terms