Browsing by Author "Girard, Timothy D."

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    Chronic neuropsychiatric sequelae of SARS-CoV-2: Protocol and methods from the Alzheimer's Association Global Consortium
    (Alzheimer’s Association, 2022-09-22) de Erausquin, Gabriel A.; Snyder, Heather; Brugha, Traolach S.; Seshadri, Sudha; Carrillo, Maria; Sagar, Rajesh; Huang, Yueqin; Newton, Charles; Tartaglia, Carmela; Teunissen, Charlotte; Håkanson, Krister; Akinyemi, Rufus; Prasad, Kameshwar; D'Avossa, Giovanni; Gonzalez-Aleman, Gabriela; Hosseini, Akram; Vavougios, George D.; Sachdev, Perminder; Bankart, John; Ole Mors, Niels Peter; Lipton, Richard; Katz, Mindy; Fox, Peter T.; Katshu, Mohammad Zia; Iyengar, M. Sriram; Weinstein, Galit; Sohrabi, Hamid R.; Jenkins, Rachel; Stein, Dan J.; Hugon, Jacques; Mavreas, Venetsanos; Blangero, John; Cruchaga, Carlos; Krishna, Murali; Wadoo, Ovais; Becerra, Rodrigo; Zwir, Igor; Longstreth, William T.; Kroenenberg, Golo; Edison, Paul; Mukaetova-Ladinska, Elizabeta; Staufenberg, Ekkehart; Figueredo-Aguiar, Mariana; Yécora, Agustín; Vaca, Fabiana; Zamponi, Hernan P.; Lo Re, Vincenzina; Majid, Abdul; Sundarakumar, Jonas; Gonzalez, Hector M.; Geerlings, Mirjam I.; Skoog, Ingmar; Salmoiraghi, Alberto; Boneschi, Filippo Martinelli; Patel, Vibuthi N.; Santos, Juan M.; Arroyo, Guillermo Rivera; Moreno, Antonio Caballero; Felix, Pascal; Gallo, Carla; Arai, Hidenori; Yamada, Masahito; Iwatsubo, Takeshi; Sharma, Malveeka; Chakraborty, Nandini; Ferreccio, Catterina; Akena, Dickens; Brayne, Carol; Maestre, Gladys; Williams Blangero, Sarah; Brusco, Luis I.; Siddarth, Prabha; Hughes, Timothy M.; Ramírez Zuñiga, Alfredo; Kambeitz, Joseph; Laza, Agustin Ruiz; Allen, Norrina; Panos, Stella; Merrill, David; Ibáñez, Agustín; Tsuang, Debby; Valishvili, Nino; Shrestha, Srishti; Wang, Sophia; Padma, Vasantha; Anstey, Kaarin J.; Ravindrdanath, Vijayalakshmi; Blennow, Kaj; Mullins, Paul; Łojek, Emilia; Pria, Anand; Mosley, Thomas H.; Gowland, Penny; Girard, Timothy D.; Bowtell, Richard; Vahidy, Farhaan S.; Psychiatry, School of Medicine
    Introduction: Coronavirus disease 2019 (COVID-19) has caused >3.5 million deaths worldwide and affected >160 million people. At least twice as many have been infected but remained asymptomatic or minimally symptomatic. COVID-19 includes central nervous system manifestations mediated by inflammation and cerebrovascular, anoxic, and/or viral neurotoxicity mechanisms. More than one third of patients with COVID-19 develop neurologic problems during the acute phase of the illness, including loss of sense of smell or taste, seizures, and stroke. Damage or functional changes to the brain may result in chronic sequelae. The risk of incident cognitive and neuropsychiatric complications appears independent from the severity of the original pulmonary illness. It behooves the scientific and medical community to attempt to understand the molecular and/or systemic factors linking COVID-19 to neurologic illness, both short and long term. Methods: This article describes what is known so far in terms of links among COVID-19, the brain, neurological symptoms, and Alzheimer's disease (AD) and related dementias. We focus on risk factors and possible molecular, inflammatory, and viral mechanisms underlying neurological injury. We also provide a comprehensive description of the Alzheimer's Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2) harmonized methodology to address these questions using a worldwide network of researchers and institutions. Results: Successful harmonization of designs and methods was achieved through a consensus process initially fragmented by specific interest groups (epidemiology, clinical assessments, cognitive evaluation, biomarkers, and neuroimaging). Conclusions from subcommittees were presented to the whole group and discussed extensively. Presently data collection is ongoing at 19 sites in 12 countries representing Asia, Africa, the Americas, and Europe. Discussion: The Alzheimer's Association Global Consortium harmonized methodology is proposed as a model to study long-term neurocognitive sequelae of SARS-CoV-2 infection. Key points: The following review describes what is known so far in terms of molecular and epidemiological links among COVID-19, the brain, neurological symptoms, and AD and related dementias (ADRD)The primary objective of this large-scale collaboration is to clarify the pathogenesis of ADRD and to advance our understanding of the impact of a neurotropic virus on the long-term risk of cognitive decline and other CNS sequelae. No available evidence supports the notion that cognitive impairment after SARS-CoV-2 infection is a form of dementia (ADRD or otherwise). The longitudinal methodologies espoused by the consortium are intended to provide data to answer this question as clearly as possible controlling for possible confounders. Our specific hypothesis is that SARS-CoV-2 triggers ADRD-like pathology following the extended olfactory cortical network (EOCN) in older individuals with specific genetic susceptibility. The proposed harmonization strategies and flexible study designs offer the possibility to include large samples of under-represented racial and ethnic groups, creating a rich set of harmonized cohorts for future studies of the pathophysiology, determinants, long-term consequences, and trends in cognitive aging, ADRD, and vascular disease. We provide a framework for current and future studies to be carried out within the Consortium. and offers a "green paper" to the research community with a very broad, global base of support, on tools suitable for low- and middle-income countries aimed to compare and combine future longitudinal data on the topic. The Consortium proposes a combination of design and statistical methods as a means of approaching causal inference of the COVID-19 neuropsychiatric sequelae. We expect that deep phenotyping of neuropsychiatric sequelae may provide a series of candidate syndromes with phenomenological and biological characterization that can be further explored. By generating high-quality harmonized data across sites we aim to capture both descriptive and, where possible, causal associations.
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    A Multisite Study of Nurse-Reported Perceptions and Practice of ABCDEF Bundle Components
    (Elsevier, 2020-10) Boehm, Leanne M.; Pun, Brenda T.; Stollings, Joanna L.; Girard, Timothy D.; Rock, Peter; Hough, Catherine L.; Hsieh, S. Jean; Khan, Babar A.; Owens, Robert L.; Schmidt, Gregory A.; Smith, Susan; Ely, E. Wesley; Medicine, School of Medicine
    Objectives: ABCDEF bundle implementation in the Intensive Care Unit (ICU) is associated with dose dependent improvements in patient outcomes. The objective was to compare nurse attitudes about the ABCDEF bundle to self-reported adherence to bundle components. Research methodology/design: Cross-sectional study. Setting: Nurses providing direct patient care in 28 ICUs within 18 hospitals across the United States. Main outcome measures: 53-item survey of attitudes and practice of the ABCDEF bundle components was administered between November 2011 and August 2015 (n = 1661). Results: We did not find clinically significant correlations between nurse attitudes and adherence to Awakening trials, Breathing trials, and sedation protocol adherence (rs = 0.05-0.28) or sedation plan discussion during rounds and Awakening and Breathing trial Coordination (rs = 0.19). Delirium is more likely to be discussed during rounds when ICU physicians and nurse managers facilitate delirium reduction (rs = 0.27-0.36). Early mobilization is more likely to occur when ICU physicians, nurse managers, staffing, equipment, and the ICU environment facilitate early mobility (rs = 0.36-0.47). Physician leadership had the strongest correlation with reporting an ICU environment that facilitates ABCDEF bundle implementation (rs = 0.63-0.74). Conclusions: Nurse attitudes about bundle implementation did not predict bundle adherence. Nurse manager and physician leadership played a large role in creating a supportive ICU environment.
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    Post-Intensive Care Syndrome and Caregiver Burden: A Post Hoc Analysis of a Randomized Clinical Trial
    (American Medical Association, 2025-04-01) Ahn, Soojung; LaNoue, Marianna; Su, Han; Moale, Amanda C.; Scheunemann, Leslie P.; Kiehl, Amy L.; Douglas, Ivor S.; Exline, Matthew C.; Gong, Michelle N.; Khan, Babar A.; Owens, Robert L.; Pisani, Margaret A.; Rock, Peter; Jackson, James C.; Ely, E. Wesley; Girard, Timothy D.; Boehm, Leanne M.; Medicine, School of Medicine
    Importance: Understanding the reciprocal association between post-intensive care syndrome (PICS) and caregiver burden is crucial for optimal care of patients and caregivers following critical illness. Objective: To evaluate the associations between patient post-intensive care impairments and caregiver burden. Design, setting, and participants: This secondary analysis of the MIND-USA study, a multicenter randomized clinical trial, which enrolled patients admitted to intensive care units (ICU) from 16 academic medical centers across the US (December 2011 to August 2017), included 148 patient-caregiver dyads. Patients were adults aged 18 years or older with ICU delirium randomized to receive haloperidol, ziprasidone, or placebo. A caregiver who provided unpaid assistance to the patient was identified at enrollment. PICS and caregiver burden were assessed at 3 months and 12 months after randomization. Statistical analysis was performed from March 2023 to April 2024. Main outcomes and measures: ICU survivors were assessed for PICS domains, including physical and cognitive function, and posttraumatic stress disorder using the Katz Activities of Daily Living, the Functional Activities Questionnaire, the Telephone Interview for Cognitive Status, and the Posttraumatic Stress Disorder Checklist-Civilian version, respectively. Caregiver burden was assessed using the Zarit Burden Interview. The associations between patient PICS and caregiver burden at 3 and 12 months were examined using structural equation modeling. Results: Of 148 patients included in this study with a median (IQR) age of 58 (48-65) years, the majority identified as male (79 patients [53.4%]), and there were 16 (10.8%) Black, 139 (93.9%) non-Hispanic, and 127 (85.8%) White patients. PICS and caregiver burden at 3-month follow-up was positively associated with these outcomes at 12-month follow-up (PICS: β = 0.69; 95% CI, 0.50 to 0.88; P < .001; caregiver burden: β = 0.68; 95% CI, 0.53 to 0.82; P < .001). However, contrary to the study hypotheses, significant associations between 3-month PICS and 12-month caregiver burden and between 3-month caregiver burden and 12-month PICS were not observed (PICS→caregiver burden: β = 0.82; 95% CI, -0.02 to 1.66; P = .09; caregiver burden→PICS: β = 0.00; 95% CI, -0.03 to 0.03; P = .95). There was significant covariance between PICS and caregiver burden at each time point. Conclusions and relevance: In this secondary analysis of a randomized clinical trial of ICU survivors and their caregivers, patient PICS and caregiver burden were associated at concurrent time points but were not associated with each other longitudinally.
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    Reporting Essentials for DElirium bioMarker Studies (REDEEMS): Explanation and Elaboration
    (European Delirium Association, 2022-12-21) Amgarth-Duff, Ingrid; Hosie, Annemarie; Caplan, Gideon A.; Adamis, Dimitrios; Watne, Leiv Otto; Cunningham, Colm; Oh, Esther S.; Wang, Sophia; Lindroth, Heidi; Sanders, Robert D.; Olofsson, Birgitta; Girard, Timothy D.; Steiner, Luzius A.; Vasunilashorn, Sarinnapha M.; Agar, Meera; Psychiatry, School of Medicine
    Despite many studies of potential delirium biomarkers, delirium pathophysiology remains unclear. Evidence shows that the quality of reporting delirium biomarker studies is sub-optimal. Better reporting of delirium biomarker studies is needed to understand delirium pathophysiology better. To improve robustness, transparency and uniformity of delirium biomarker study reports, the REDEEMS (Reporting Essentials for DElirium bioMarker Studies) guideline was developed by an international group of delirium researchers through a three-stage process, including a systematic review, a three-round Delphi study, and a follow-up consensus meeting. This process resulted in a 9-item guideline to inform delirium fluid biomarker studies. To enhance implementation of the REDEEMS guideline, this Explanation and Elaboration paper provides a detailed explanation of each item. We anticipate that the REDEEMS guideline will help to accelerate our understanding of delirium pathophysiology by improving the reporting of delirium biomarker research and, consequently the capacity to synthesise results across studies.