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  1. Article ; Online: Acetylcysteine for the Treatment of Suspected Remdesivir-Associated Acute Liver Failure in COVID-19: A Case Series.

    Carothers, Chancey / Birrer, Kara / Vo, Mai

    Pharmacotherapy

    2020  Volume 40, Issue 11, Page(s) 1166–1171

    Abstract: Remdesivir is a direct-acting nucleoside RNA polymerase inhibitor with activity against the novel severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) virus used in the treatment of coronavirus disease 2019 (COVID-19) pneumonia. Here, we present ... ...

    Abstract Remdesivir is a direct-acting nucleoside RNA polymerase inhibitor with activity against the novel severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) virus used in the treatment of coronavirus disease 2019 (COVID-19) pneumonia. Here, we present two cases of suspected remdesivir-associated acute liver failure (ALF) in which the liver failure improved after continuous infusion acetylcysteine and withdrawal of remdesivir. Both patients had significant increases in transaminases between day 3 and day 10 of remdesivir therapy accompanied by coagulopathy and encephalopathy. After initiation of continuous infusion acetylcysteine, the transaminases of both patients rapidly improved. Ultimately, one patient fully recovered while the other died of suspected septic shock. Due to its novel nature and only recent widespread use, there are very little data on the risk of ALF from remdesivir. Additionally, the data for the use of acetylcysteine to manage non-acetaminophen-induced ALF are limited. It is important to consider the risk of remdesivir-associated ALF when weighing the risk versus benefits of use, and acetylcysteine may have a role in its management.
    MeSH term(s) Acetylcysteine/administration & dosage ; Acetylcysteine/therapeutic use ; Adenosine Monophosphate/administration & dosage ; Adenosine Monophosphate/adverse effects ; Adenosine Monophosphate/analogs & derivatives ; Adenosine Monophosphate/therapeutic use ; Aged ; Aged, 80 and over ; Alanine/administration & dosage ; Alanine/adverse effects ; Alanine/analogs & derivatives ; Alanine/therapeutic use ; Antiviral Agents/administration & dosage ; Antiviral Agents/adverse effects ; Antiviral Agents/therapeutic use ; COVID-19/drug therapy ; Fatal Outcome ; Female ; Humans ; Liver Failure, Acute/chemically induced ; Liver Failure, Acute/diagnosis ; Liver Failure, Acute/drug therapy ; Liver Function Tests ; SARS-CoV-2 ; Treatment Outcome
    Chemical Substances Antiviral Agents ; remdesivir (3QKI37EEHE) ; Adenosine Monophosphate (415SHH325A) ; Alanine (OF5P57N2ZX) ; Acetylcysteine (WYQ7N0BPYC)
    Keywords covid19
    Language English
    Publishing date 2020-10-27
    Publishing country United States
    Document type Case Reports
    ZDB-ID 603158-4
    ISSN 1875-9114 ; 0277-0008
    ISSN (online) 1875-9114
    ISSN 0277-0008
    DOI 10.1002/phar.2464
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Prevalence and Risk Factors for Iatrogenic Opioid Withdrawal in Medical Critical Care Patients.

    Fox, Marlena A / Carothers, Chancey / Dircksen, Katie K / Birrer, Kara L / Choi, Min J / Mukkera, Satyanarayana R

    Critical care explorations

    2023  Volume 5, Issue 5, Page(s) e0904

    Abstract: Opioids are the mainstay of pain management and sedation in critically ill patients, which can lead to the development of physiologic tolerance and dependency. The prevalence of iatrogenic opioid withdrawal syndrome (IWS) is reported as 17-32% in the ICU; ...

    Abstract Opioids are the mainstay of pain management and sedation in critically ill patients, which can lead to the development of physiologic tolerance and dependency. The prevalence of iatrogenic opioid withdrawal syndrome (IWS) is reported as 17-32% in the ICU; however, limited evidence exists for the medical ICU patient population.
    Objectives: To identify the and risk factors for IWS in adult patients admitted to critical care medicine services who received greater than or equal to 24 hours of continuous opioid infusion therapy.
    Design setting and participants: A prospective, observational study was conducted in a tertiary care hospital in adult medical ICU patients. Ninety-two patients who received greater than or equal to 24 hours of continuous opioid infusions were included in the study.
    Main outcomes and measurements: Patients were assessed daily after opioid infusion discontinuation using the Clinical Opiate Withdrawal Scale (COWS) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) opioid withdrawal criteria for a maximum of 5 days. The primary outcome was the prevalence of IWS of moderate severity or greater using COWS. Secondary outcomes included the prevalence of IWS diagnosis of any severity based on COWS, the prevalence of IWS diagnosis based on a positive DSM-V score, and the identification of potential risk factors for developing IWS of any severity.
    Results: Four hundred forty-seven patients received greater than or equal to 24 hours of continuous opioid therapy. Of these, 385 were excluded, leaving 92 patients included in the final analysis. Except for a higher prevalence of psychiatric history in the IWS-positive group, baseline characteristics were similar. Overall, 11 patients (12%) developed IWS of moderate severity or greater, based on COWS. The IWS-positive group also had longer durations of opioid infusions, higher cumulative opioid infusion doses, higher mean daily doses, and higher infusion rates at any given time. The concomitant use of dexmedetomidine (38.3 vs 15.6%,
    Conclusions and relevance: Approximately one in every eight patients receiving continuous infusion opioid for greater than 24 hours while mechanically ventilated in the medical ICU will develop IWS of moderate severity or greater; this increases to one in three patients diagnosed with DSM-V criteria or any level of IWS severity. Patients receiving opioid infusions greater than or equal to 72 hours, or a total daily fentanyl dose of greater than or equal to 1,200 μg (~ 50 μg/hr) are at a higher risk for developing IWS and should be monitored as part of clinical practice when opioid infusions are discontinued.
    Language English
    Publishing date 2023-05-03
    Publishing country United States
    Document type Journal Article
    ISSN 2639-8028
    ISSN (online) 2639-8028
    DOI 10.1097/CCE.0000000000000904
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Acetylcysteine for the Treatment of Suspected Remdesivir‐Associated Acute Liver Failure in COVID‐19

    Carothers, Chancey / Birrer, Kara / Vo, Mai

    Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy ; ISSN 0277-0008 1875-9114

    A Case Series

    2020  

    Keywords Pharmacology (medical) ; covid19
    Language English
    Publisher Wiley
    Publishing country us
    Document type Article ; Online
    DOI 10.1002/phar.2464
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article: Acetylcysteine for the Treatment of Suspected Remdesivir-Associated Acute Liver Failure in COVID-19: A Case Series

    Carothers, Chancey / Birrer, Kara / Vo, Mai

    Pharmacotherapy

    Abstract: Remdesivir is a direct-acting nucleoside RNA polymerase inhibitor with activity against the novel severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) virus used in the treatment of coronavirus disease 2019 (COVID-19) pneumonia. Here, we present ... ...

    Abstract Remdesivir is a direct-acting nucleoside RNA polymerase inhibitor with activity against the novel severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) virus used in the treatment of coronavirus disease 2019 (COVID-19) pneumonia. Here, we present two cases of suspected remdesivir-associated acute liver failure (ALF) in which the liver failure improved after continuous infusion acetylcysteine and withdrawal of remdesivir. Both patients had significant increases in transaminases between day 3 and day 10 of remdesivir therapy accompanied by coagulopathy and encephalopathy. After initiation of continuous infusion acetylcysteine, the transaminases of both patients rapidly improved. Ultimately, one patient fully recovered while the other died of suspected septic shock. Due to its novel nature and only recent widespread use, there are very little data on the risk of ALF from remdesivir. Additionally, the data for the use of acetylcysteine to manage non-acetaminophen-induced ALF are limited. It is important to consider the risk of remdesivir-associated ALF when weighing the risk versus benefits of use, and acetylcysteine may have a role in its management.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #33006138
    Database COVID19

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  5. Article ; Online: Activated prothrombin complex concentrate for warfarin reversal in traumatic intracranial hemorrhage.

    Carothers, Chancey / Giancarelli, Amanda / Ibrahim, Joseph / Hobbs, Brandon

    The Journal of surgical research

    2017  Volume 223, Page(s) 183–187

    Abstract: Background: Patients with traumatic intracranial hemorrhage (TIH) anticoagulated with warfarin are at an increased risk of mortality. Fresh frozen plasma (FFP) and vitamin K have been the standard treatment for warfarin reversal; however, guidelines now ...

    Abstract Background: Patients with traumatic intracranial hemorrhage (TIH) anticoagulated with warfarin are at an increased risk of mortality. Fresh frozen plasma (FFP) and vitamin K have been the standard treatment for warfarin reversal; however, guidelines now recommend the use of prothrombin complex concentrate (PCC) for warfarin reversal in patients with life-threatening bleeding. Our protocol uses one vial (∼1000 units) of activated PCC (aPCC) for warfarin reversal, regardless of the weight or presenting international normalized ratio (INR). The purpose of this study was to determine the safety and efficacy of using fixed, low-dose aPCC for warfarin reversal in patients with TIH.
    Methods: This was a retrospective chart review that included patients with an Abbreviated Injury Scale Head score of ≥3, TIH, and initial INR ≥ 1.5 on warfarin. Patients aged <18 years and those with no repeat INR were excluded. The primary outcome was to compare the percentage of patients with INR ≤ 1.4 after receiving aPCC versus FFP within 24 hours.
    Results: Eighty-nine patients were in the FFP group and 31 patients in the aPCC group. The INR was reversed more effectively in the aPCC group compared with the FFP group (90.3% versus 69.7%, P = 0.029). The median time (hours) to reversal was also significantly shorter in the aPCC group compared with the FFP group (3.75 versus 6.75, P = 0.003). However, there was no difference in mortality (35.5% aPCC versus 22.2% control, P = 0.162) or incidences of thrombosis.
    Conclusion: Fixed, low-dose aPCC is safe and more effective at reversing the effects of warfarin than FFP in patients with TIH.
    MeSH term(s) Aged ; Aged, 80 and over ; Blood Coagulation Factors/therapeutic use ; Female ; Humans ; International Normalized Ratio ; Intracranial Hemorrhage, Traumatic/drug therapy ; Male ; Retrospective Studies ; Warfarin/antagonists & inhibitors
    Chemical Substances Blood Coagulation Factors ; prothrombin complex concentrates (37224-63-8) ; Warfarin (5Q7ZVV76EI)
    Language English
    Publishing date 2017-12-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80170-7
    ISSN 1095-8673 ; 0022-4804
    ISSN (online) 1095-8673
    ISSN 0022-4804
    DOI 10.1016/j.jss.2017.11.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Book ; Online: New Visions of Collective Achievement

    Carothers, Suzanne C / Hucks, Darrell Cleveland

    The Cross-Generational Schooling Experiences of African American Males

    2014  

    Abstract: ... who work with this population to show the value of education in the African American community.” - Chance W. Lewis, Ph.D. Carol ...

    Author's details by Suzanne C. Carothers, Darrell Cleveland Hucks
    Abstract New Visions of Collective Achievement: The Cross-Generational Schooling Experiences of African American Males takes you on a journey into the lives of three families of African American males, each with an elementary aged boy. Bear witness to each boy’s observations and insights on his current schooling experiences, also hear what older males in his family have to say regarding their schooling experiences. Employing qualitative methodology to include their frequently unheard voices in educational research, this book endeavors to move toward correcting this oversight. New Visions of Collective Achievement graciously offers each of us, as stakeholders, a most precious gift: a theoretical and practical framework to effect real, meaningful, and long-lasting change if we are courageous enough to take heed. “This refreshingly clear and focused book presents a comprehensive discussion on the schooling experiences of African American males across generations. This invaluable resource should be required reading for all educators who work with this population to show the value of education in the African American community.” - Chance W. Lewis, Ph.D. Carol Grotnes Belk Distinguished Professor of Urban Education, UNC Charlotte “New Visions of Collective Achievement provides educators with an important insight into the ways Black males experience their education across time. Through groundbreaking research presented in the voices of three generations of Black males, this book commands attention and calls for multiple stakeholders in our schools and communities to work together to cultivate and advance the social and academic well-being of Black males.” - Yolanda Sealey-Ruiz, Ph.D. Assistant Professor of English Education, Teachers College, Columbia University “New Visions encapsulates the spirit of African American males who are separated by generations, yet bound by a collective struggle against social injustice and a desire for success. Dr. Hucks invokes a reverence for historical oppression, an awareness of present day opportunities and barriers, and a visionary path for future generations of Black men.” - Ivory A. Toldson, Ph.D. Editor-in-Chief, The Journal of Negro Education; Associate Professor, Counseling Psychology Program, Howard University
    Keywords Education ; Psychologie / Pädagogik Pädagogik
    Language English
    Size Online-Ressource (XX, 150 p), online resource
    Publisher SensePublishers
    Publishing place Rotterdam ;s.l
    Document type Book ; Online
    Note Includes bibliographical references (pages 141-145) and index
    ISBN 9789462098091 ; 9462098093
    DOI 10.1007/978-94-6209-809-1
    Database Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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  7. Article ; Online: Evaluation of the Implementation Research Institute: Trainees' Publications and Grant Productivity.

    Baumann, Ana A / Carothers, Bobbi J / Landsverk, John / Kryzer, Emily / Aarons, Gregory A / Brownson, Ross C / Glisson, Charles / Mittman, Brian / Proctor, Enola K

    Administration and policy in mental health

    2019  Volume 47, Issue 2, Page(s) 254–264

    Abstract: ... year out and increasing to 94% for those who were 4 years out from starting training. Chances for Non ...

    Abstract With growth in the field of dissemination and implementation (D&I) research, there has been growth in capacity building, with many training opportunities. As such, it is important to continue to evaluate D&I research training programs. This paper reports the results of an evaluation of the Implementation Research Institute (IRI), a R25 funded by the National Institute of Mental Health with additional funding by the Department of Veterans Affairs (VA). The fourth cohort also had a supplement from the National Institute on Drug Abuse. Using bibliometrics data, we report on a quasi-experimental retrospective cohort study assessing whether the rates of scholarly productivity in D&I science of IRI fellows (those who applied and were accepted to the training) were greater than those who applied but were not accepted to IRI. Our findings show that Selected Applicants' odds of publishing in implementation science were higher for earlier alumni, starting at 12% 1 year out and increasing to 94% for those who were 4 years out from starting training. Chances for Non-Selected Applicants remained relatively stable, starting at 47% at 1 year and going to 33% at 4 years since their application, a pattern that was stable even after controlling for demographic characteristics. These results support the hypothesis that IRI is increasing the D&I research productivity of those selected to the program, and that our fellows are advancing the field of D&I compared to those investigators not selected to our institute. Our finding also indicates the importance of a 2-year training.
    MeSH term(s) Academies and Institutes/statistics & numerical data ; Bibliometrics ; Biomedical Research ; Financing, Organized/statistics & numerical data ; Humans ; Implementation Science ; Information Dissemination/methods ; Periodicals as Topic/statistics & numerical data ; Research Personnel/education ; Retrospective Studies ; Translational Research, Biomedical/education ; United States
    Language English
    Publishing date 2019-08-31
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1025319-1
    ISSN 1573-3289 ; 0894-587X
    ISSN (online) 1573-3289
    ISSN 0894-587X
    DOI 10.1007/s10488-019-00977-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Use of computer simulation to evaluate a putative cluster of genetic or teratologic outcomes: adjustment for "multiple hypotheses" and application to a reported excess of Down's syndrome.

    Hook, E B / Carothers, A D

    Genetic epidemiology

    1997  Volume 14, Issue 2, Page(s) 133–145

    Abstract: ... statistical significance, is due to chance concatenation of events or to an environmental factor ... probability that it arose by chance. ...

    Abstract The identification of an apparent excess of a genetic outcome in a particular area and/or a particular time often provokes considerable public alarm about the presence of an environmental mutagen. It is often difficult to determine in any particular case whether the observation, whatever its nominal statistical significance, is due to chance concatenation of events or to an environmental factor. Statistical evaluation is made more difficult by the profuse number of possible hypotheses that could have triggered concern about an excess. This renders it difficult to calculate the actual probability of the observation (or one more extreme). By attempting to identify similar types of outcomes that could have provoked an apparent excess and then undertaking computer simulations assuming random deviations from a constant rate, one may attempt to adjust for the problem of multiple hypotheses. We apply this approach to a reported excess of Down's syndrome in Norway in 1985-1986 in younger mothers, and conclude that there is a high probability that it arose by chance.
    MeSH term(s) Adolescent ; Adult ; Cluster Analysis ; Computer Simulation ; Down Syndrome/epidemiology ; Down Syndrome/genetics ; Female ; Humans ; Maternal Age ; Middle Aged ; Models, Genetic ; Norway/epidemiology ; Population Surveillance ; Pregnancy ; Pregnancy Outcome/epidemiology ; Pregnancy Outcome/genetics ; Pregnancy, High-Risk ; Retrospective Studies ; Teratology/statistics & numerical data
    Language English
    Publishing date 1997
    Publishing country United States
    Document type Journal Article
    ZDB-ID 605785-8
    ISSN 1098-2272 ; 0741-0395
    ISSN (online) 1098-2272
    ISSN 0741-0395
    DOI 10.1002/(SICI)1098-2272(1997)14:2<133::AID-GEPI3>3.0.CO;2-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Strategy for mapping quantitative trait loci (QTL) by using human metapopulations.

    Rudan, Igor / Biloglav, Zrinka / Carothers, Andrew D / Wright, Alan F / Campbell, Harry

    Croatian medical journal

    2006  Volume 47, Issue 4, Page(s) 532–542

    Abstract: ... of standardized QT measurement distribution was found 10 times more frequently than expected by chance. The large ...

    Abstract Aim: To present a novel strategy for mapping quantitative trait loci (QTL), using human metapopulations. The strategy is based on the expectation that in geographic clusters of small and distinct human isolates, a combination of founder effect and genetic drift can dramatically increase population frequency of rare QTL variants with large effect. In such cases, the distribution of QT measurements in an (affected) isolate is expected to deviate from that observed in neighboring isolates.
    Methods: We tested this hypothesis in 9 villages from a larger Croatian isolate resource, where 7 Mendelian disorders have been previously reported. The values of 10 physiological and biochemical QTs were measured in a random sample of 1001 individuals (100 inhabitants of each of 9 villages and 101 immigrant controls).
    Results: Significant over- or under- representation of individuals from specific villages in extreme ends of standardized QT measurement distribution was found 10 times more frequently than expected by chance. The large majority of such clusters of individuals with extreme QT values (34/36, 94.4%) originated from the 6 villages with the most pronounced geographic isolation and endogamy.
    Conclusion: Early epidemiological assessment supports the feasibility of the proposed strategy. Clusters of individuals with extreme QT values responsible for over-representation of single villages can usually be linked to a larger pedigree and may be useful for further QTL mapping, using linkage analysis.
    MeSH term(s) Body Height ; Chromosome Mapping ; Croatia ; Dwarfism/genetics ; Female ; Gene Frequency ; Genetics, Population ; Geography ; Humans ; Male ; Models, Genetic ; Quantitative Trait Loci
    Language English
    Publishing date 2006-08-15
    Publishing country Croatia
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1157623-6
    ISSN 1332-8166 ; 0353-9504
    ISSN (online) 1332-8166
    ISSN 0353-9504
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Association within a family of a balanced autosomal translocation with major mental illness.

    St Clair, D / Blackwood, D / Muir, W / Carothers, A / Walker, M / Spowart, G / Gosden, C / Evans, H J

    Lancet (London, England)

    1990  Volume 336, Issue 8706, Page(s) 13–16

    Abstract: ... without it. The lod scores (against chance linkage of the translocation with mental illness) were greatest ...

    Abstract 282 pedigrees in the MRC Cytogenetics Registry, Edinburgh, with familial autosomal anomalies were examined for the presence of associated mental illness. In one large pedigree there were 23 cases of mental and/or behavioural disorders meeting Research Diagnostic Criteria. 34 of the 77 family members available for cytogenetic analysis carried a balanced translocation t(1:11) (q43,q21). Psychiatric diagnoses had been recorded for 16 of the 34 members with the translocation compared with only 5 of the 43 without it. The lod scores (against chance linkage of the translocation with mental illness) were greatest when the mental disorders in the phenotype were restricted to schizophrenia, schizoaffective disorder, recurrent major depression, and adolescent conduct and emotional disorders. Although the mental illness in this family may not be typical of that in the general population, the findings suggest that the q21-22 region of chromosome 11 may be a promising area to examine for genes predisposing to major mental illness.
    MeSH term(s) Adolescent ; Adult ; Child ; Chromosome Aberrations/genetics ; Chromosome Disorders ; Chromosome Mapping ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 11 ; Disease Susceptibility ; Female ; Genetic Linkage ; Humans ; Lod Score ; Male ; Mental Disorders/epidemiology ; Mental Disorders/genetics ; Odds Ratio ; Pedigree ; Phenotype ; Registries ; Scotland/epidemiology ; Translocation, Genetic
    Language English
    Publishing date 1990-07-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3306-6
    ISSN 1474-547X ; 0140-6736 ; 0023-7507
    ISSN (online) 1474-547X
    ISSN 0140-6736 ; 0023-7507
    DOI 10.1016/0140-6736(90)91520-k
    Database MEDical Literature Analysis and Retrieval System OnLINE

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