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  1. Article ; Online: How to Rapidly Determine First-in-Children Dosing for COVID-19 Therapeutics.

    Watt, Kevin M

    JAMA pediatrics

    2020  Volume 174, Issue 10, Page(s) e202435

    MeSH term(s) Betacoronavirus ; COVID-19 ; Child ; Coronavirus ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; SARS-CoV-2 ; Therapies, Investigational
    Keywords covid19
    Language English
    Publishing date 2020-10-05
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 2701223-2
    ISSN 2168-6211 ; 2168-6203
    ISSN (online) 2168-6211
    ISSN 2168-6203
    DOI 10.1001/jamapediatrics.2020.2435
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  3. Article ; Online: How to Rapidly Determine First-in-Children Dosing for COVID-19 Therapeutics

    Watt, Kevin M.

    JAMA Pediatrics

    2020  Volume 174, Issue 10, Page(s) e202435

    Keywords Pediatrics, Perinatology, and Child Health ; covid19
    Language English
    Publisher American Medical Association (AMA)
    Publishing country us
    Document type Article ; Online
    ZDB-ID 2701223-2
    ISSN 2168-6211 ; 2168-6203
    ISSN (online) 2168-6211
    ISSN 2168-6203
    DOI 10.1001/jamapediatrics.2020.2435
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Delirium in the NICU.

    Tarrell, Ariel / Giles, Lisa / Smith, Brian / Traube, Chani / Watt, Kevin

    Journal of perinatology : official journal of the California Perinatal Association

    2023  Volume 44, Issue 2, Page(s) 157–163

    Abstract: Delirium in the NICU is an underrecognized phenomenon in infants who are often complex and critically ill. The current understanding of NICU delirium is developing and can be informed by adult and pediatric literature. The NICU population faces many ... ...

    Abstract Delirium in the NICU is an underrecognized phenomenon in infants who are often complex and critically ill. The current understanding of NICU delirium is developing and can be informed by adult and pediatric literature. The NICU population faces many potential risk factors for delirium, including young age, developmental delay, mechanical ventilation, severe illness, and surgery. There are no diagnostic tools specific to infants. The mainstay of delirium treatment is to treat the underlying cause, address modifiable risk factors, and supportive care. This review will summarize current knowledge and areas where more research is needed.
    MeSH term(s) Infant ; Infant, Newborn ; Adult ; Child ; Humans ; Delirium/diagnosis ; Delirium/etiology ; Delirium/therapy ; Intensive Care Units, Neonatal ; Critical Illness ; Respiration, Artificial/adverse effects ; Risk Factors
    Language English
    Publishing date 2023-09-08
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 645021-0
    ISSN 1476-5543 ; 0743-8346
    ISSN (online) 1476-5543
    ISSN 0743-8346
    DOI 10.1038/s41372-023-01767-5
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  5. Article ; Online: Antifungal Dosing in Critically Ill Patients on Extracorporeal Membrane Oxygenation.

    Lyster, Haifa / Shekar, Kiran / Watt, Kevin / Reed, Anna / Roberts, Jason A / Abdul-Aziz, Mohd-Hafiz

    Clinical pharmacokinetics

    2023  Volume 62, Issue 7, Page(s) 931–942

    Abstract: Extracorporeal membrane oxygenation (ECMO) is an established advanced life support system, providing temporary cardiac and/or respiratory support in critically ill patients. Fungal infections are associated with increased mortality in patients on ECMO. ... ...

    Abstract Extracorporeal membrane oxygenation (ECMO) is an established advanced life support system, providing temporary cardiac and/or respiratory support in critically ill patients. Fungal infections are associated with increased mortality in patients on ECMO. Antifungal drug dosing for critically ill patients is highly challenging because of altered pharmacokinetics (PK). PK changes during critical illness; in particular, the drug volume of distribution (V
    MeSH term(s) Humans ; Antifungal Agents/pharmacokinetics ; Extracorporeal Membrane Oxygenation ; Critical Illness/therapy ; Drug Monitoring ; Anti-Bacterial Agents/pharmacokinetics
    Chemical Substances Antifungal Agents ; Anti-Bacterial Agents
    Language English
    Publishing date 2023-06-10
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 197627-8
    ISSN 1179-1926 ; 0312-5963
    ISSN (online) 1179-1926
    ISSN 0312-5963
    DOI 10.1007/s40262-023-01264-0
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    Zs.A 1246: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
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  6. Article ; Online: Medication patterns and dosing guidance in pediatric patients supported with intermittent hemodialysis or continuous kidney replacement therapy.

    McKnite, Autumn M / Green, Danielle J / Nelson, Raoul / Brewer, Simon C / Watt, Kevin M

    Pediatric nephrology (Berlin, Germany)

    2023  Volume 39, Issue 5, Page(s) 1521–1532

    Abstract: Background: Hemodialysis is a life-saving technology used during periods of acute or chronic kidney failure to remove toxins, and maintain fluid, electrolyte and metabolic balance. While this technology plays an important role for pediatric patients ... ...

    Abstract Background: Hemodialysis is a life-saving technology used during periods of acute or chronic kidney failure to remove toxins, and maintain fluid, electrolyte and metabolic balance. While this technology plays an important role for pediatric patients with kidney dysfunction, it can alter the pharmacokinetic behavior of medications placing patients at risk for suboptimal dosing and drug toxicity. The ability to directly translate pharmacokinetic alterations into dosing recommendations has thus far been limited and dosing guidance specific to pediatric hemodialysis patients is rare. Despite differences in dialysis prescription and patient populations, intermittent (iHD) and continuous kidney replacement therapy (CKRT) patients are often pooled together. In order to develop evidence-based dosing guidelines, it is important to first prioritize drugs for study in each modality.
    Methods: Here we aim to identify priority drugs in two hemodialysis modalities, through: 1) Identification of hospitalized, pediatric patients who received CKRT or intermittent hemodialysis (iHD) using a machine learning-based predictive model based on medications; 2) Identification of medication administration patterns in these patient cohorts; and 3) Identification of the most commonly prescribed drugs that lack published dosing guidance.
    Results: Notable differences were found in the pattern of medications and drug dosing guidance between iHD and CKRT patients. Antibiotics, diuretics and sedatives were more common in CKRT patients. Out of the 50 most commonly administered medications in the two modalities, only 34% and 28% had dosing guidance present for iHD and CKRT, respectively.
    Conclusions: Our results add to the understanding of the differences between iHD and CKRT patient populations by identifying commonly used medications that lack dosing guidance for each hemodialysis modality, helping to pinpoint priority medications for further study. Overall, this study provides an overview of the current limitations in medication use in this at-risk population, and provides a framework for future studies by identifying commonly used medications in pediatric CKRT and iHD patients.
    MeSH term(s) Child ; Humans ; Acute Kidney Injury/epidemiology ; Anti-Bacterial Agents/therapeutic use ; Continuous Renal Replacement Therapy ; Kidney Failure, Chronic/therapy ; Kidney Failure, Chronic/metabolism ; Pharmaceutical Preparations ; Renal Dialysis/methods ; Renal Replacement Therapy
    Chemical Substances Anti-Bacterial Agents ; Pharmaceutical Preparations
    Language English
    Publishing date 2023-12-05
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 631932-4
    ISSN 1432-198X ; 0931-041X
    ISSN (online) 1432-198X
    ISSN 0931-041X
    DOI 10.1007/s00467-023-06199-z
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    Zs.A 2196: Show issues Location:
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  7. Article ; Online: Reducing hydrophobic drug adsorption in an in-vitro extracorporeal membrane oxygenation model.

    Khurana, Nitish / Watkins, Kamiya / Ghatak, Debika / Staples, Jane / Hubbard, Oliver / Yellepeddi, Venkata / Watt, Kevin / Ghandehari, Hamidreza

    European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V

    2024  Volume 198, Page(s) 114261

    Abstract: Extracorporeal membrane oxygenation (ECMO) is a life-saving cardiopulmonary bypass technology for critically ill patients with heart and lung failure. Patients treated with ECMO receive a range of drugs that are used to treat underlying diseases and ... ...

    Abstract Extracorporeal membrane oxygenation (ECMO) is a life-saving cardiopulmonary bypass technology for critically ill patients with heart and lung failure. Patients treated with ECMO receive a range of drugs that are used to treat underlying diseases and critical illnesses. However, the dosing guidelines for these drugs used in ECMO patients are unclear. Mortality rate for patients on ECMO exceeds 40% partly due to inaccurate dosing information, caused in part by the adsorption of drugs in the ECMO circuit and its components. These drugs range in hydrophobicity, electrostatic interactions, and pharmacokinetics. Propofol is commonly administered to ECMO patients and is known to have high adsorption rates to the circuit components due to its hydrophobicity. To reduce adsorption onto the circuit components, we used micellar block copolymers (Poloxamer 188
    MeSH term(s) Humans ; Propofol ; Extracorporeal Membrane Oxygenation/adverse effects ; Extracorporeal Membrane Oxygenation/methods ; Adsorption ; Liposomes ; Heart ; Critical Illness/therapy
    Chemical Substances Propofol (YI7VU623SF) ; Liposomes
    Language English
    Publishing date 2024-03-14
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1065368-5
    ISSN 1873-3441 ; 0939-6411
    ISSN (online) 1873-3441
    ISSN 0939-6411
    DOI 10.1016/j.ejpb.2024.114261
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  8. Article: Amiodarone Extraction by the Extracorporeal Membrane Oxygenation Circuit.

    McDaniel, C Griffin / Honeycutt, C Cole / Watt, Kevin M

    The journal of extra-corporeal technology

    2021  Volume 53, Issue 1, Page(s) 68–74

    Abstract: Amiodarone is an anti-arrhythmic agent that is frequently used to treat tachycardias in critically ill adults and children. Because of physicochemical properties of amiodarone, extracorporeal membrane oxygenation (ECMO) circuits are expected to extract ... ...

    Abstract Amiodarone is an anti-arrhythmic agent that is frequently used to treat tachycardias in critically ill adults and children. Because of physicochemical properties of amiodarone, extracorporeal membrane oxygenation (ECMO) circuits are expected to extract amiodarone from circulation, increasing the risk of therapeutic failure. The present study seeks to determine amiodarone extraction by the ECMO circuit. Amiodarone was administered to three ex vivo circuit configurations (n = 3 per configuration) to determine the effect of each circuit component on drug extraction. The circuits were primed with human blood; standard amiodarone doses were administered; and serial samples were collected over 24 hours. Additional circuits were primed with crystalloid fluid to analyze the effect of blood on extraction and to investigate circuit saturation by drug. The crystalloid circuits were dosed multiple times over 72 hours, including a massive dose at 48 hours. For both setups, the flow was set to 1 L/min. Drug was added to separate tubes containing the prime solution to serve as controls. Drug concentrations were quantified with a validated assay, and drug recovery was calculated for each sample. Mean recovery for the circuits and controls were compared to correct for drug degradation over time. Amiodarone was heavily extracted by all ECMO circuit configurations. Eight hours after dosing, mean recovery in the blood prime circuits was 13.5-22.1%. In the crystalloid prime circuits, drug recovery decreased even more rapidly, with a mean recovery of 22.0% at 30 minutes. Similarly, drug recovery decreased more quickly in the crystalloid prime controls than in the blood prime controls. Saturation was not achieved in the crystalloid prime circuits, as final amiodarone concentrations were at the lower limit of quantification. The results suggest that amiodarone is rapidly extracted by the ECMO circuit and that saturation is not achieved by standard doses. In vivo circuit extraction may cause decreased drug exposure.
    MeSH term(s) Adult ; Amiodarone ; Child ; Extracorporeal Membrane Oxygenation ; Humans ; Metabolic Clearance Rate
    Chemical Substances Amiodarone (N3RQ532IUT)
    Language English
    Publishing date 2021-04-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 390977-3
    ISSN 0022-1058
    ISSN 0022-1058
    DOI 10.1182/ject-2000053
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  9. Article ; Online: Anakinra Removal by Continuous Renal Replacement Therapy: An Ex Vivo Analysis.

    Dubinsky, Samuel D J / Watt, Kevin M / Imburgia, Carina E / Mcknite, Autumn M / Hunt, J Porter / Rice, Cassandra / Rower, Joseph E / Edginton, Andrea N

    Critical care explorations

    2023  Volume 5, Issue 12, Page(s) e1010

    Abstract: Objectives: Patients with sepsis are at significant risk for multiple organ dysfunction, including the lungs and kidneys. To manage the morbidity associated with kidney impairment, continuous renal replacement therapy (CRRT) may be required. The extent ... ...

    Abstract Objectives: Patients with sepsis are at significant risk for multiple organ dysfunction, including the lungs and kidneys. To manage the morbidity associated with kidney impairment, continuous renal replacement therapy (CRRT) may be required. The extent of anakinra pharmacokinetics in CRRT remains unknown. The objectives of this study were to investigate the anakinra-circuit interaction and quantify the rate of removal from plasma.
    Design: The anakinra-circuit interaction was evaluated using a closed-loop ex vivo CRRT circuit. CRRT was performed in three phases based on the method of solute removal: 1) hemofiltration, 2) hemodialysis, and 3) hemodiafiltration. Standard control samples of anakinra were included to assess drug degradation.
    Setting: University research laboratory.
    Patients: None.
    Interventions: Anakinra was administered to the CRRT circuit and serial prefilter blood samples were collected along with time-matched control and hemofiltrate samples. Each circuit was run in triplicate to assess inter-run variability. Concentrations of anakinra in each reference fluid were measured by enzyme-linked immunosorbent assay. Transmembrane filter clearance was estimated by the product of the sieving coefficient/dialysate saturation constant and circuit flow rates.
    Measurements and main results: Removal of anakinra from plasma occurred within minutes for each CRRT modality. Average drug remaining (%) in plasma following anakinra administration was lowest with hemodiafiltration (34.9%). The average sieving coefficient was 0.34, 0.37, and 0.41 for hemodiafiltration, hemofiltration, and hemodialysis, respectively. Transmembrane clearance was fairly consistent across each modality with the highest during hemodialysis (5.53 mL/min), followed by hemodiafiltration (4.99 mL/min), and hemofiltration (3.94 mL/min). Percent drug remaining within the control samples (93.1%) remained consistent across each experiment, indicating negligible degradation within the blood.
    Conclusions: The results of this analysis are the first to demonstrate that large molecule therapeutic proteins such as anakinra, are removed from plasma with modern CRRT technology. Current dosing recommendations for patients with severe renal impairment may result in subtherapeutic anakinra concentrations in those receiving CRRT.
    Language English
    Publishing date 2023-12-14
    Publishing country United States
    Document type Journal Article
    ISSN 2639-8028
    ISSN (online) 2639-8028
    DOI 10.1097/CCE.0000000000001010
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  10. Article ; Online: Disparities in spatially variable gene calling highlight the need for benchmarking spatial transcriptomics methods.

    Charitakis, Natalie / Salim, Agus / Piers, Adam T / Watt, Kevin I / Porrello, Enzo R / Elliott, David A / Ramialison, Mirana

    Genome biology

    2023  Volume 24, Issue 1, Page(s) 209

    Abstract: Identifying spatially variable genes (SVGs) is a key step in the analysis of spatially resolved transcriptomics data. SVGs provide biological insights by defining transcriptomic differences within tissues, which was previously unachievable using RNA- ... ...

    Abstract Identifying spatially variable genes (SVGs) is a key step in the analysis of spatially resolved transcriptomics data. SVGs provide biological insights by defining transcriptomic differences within tissues, which was previously unachievable using RNA-sequencing technologies. However, the increasing number of published tools designed to define SVG sets currently lack benchmarking methods to accurately assess performance. This study compares results of 6 purpose-built packages for SVG identification across 9 public and 5 simulated datasets and highlights discrepancies between results. Additional tools for generation of simulated data and development of benchmarking methods are required to improve methods for identifying SVGs.
    MeSH term(s) Transcriptome ; Benchmarking ; Gene Expression Profiling
    Language English
    Publishing date 2023-09-18
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2040529-7
    ISSN 1474-760X ; 1474-760X
    ISSN (online) 1474-760X
    ISSN 1474-760X
    DOI 10.1186/s13059-023-03045-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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