4 research outputs found
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Standard Sedation and Sedation With Isoflurane in Mechanically Ventilated Patients With Coronavirus Disease 2019.
ObjectivesTo describe sedative and analgesic drug utilization in a cohort of critically ill patients with coronavirus disease 2019 and compare standard sedation with an alternative approach using inhaled isoflurane.DesignThis was a retrospective cohort study designed to compare doses of sedatives between ICU patients receiving standard IV sedation and patients receiving mixed sedation including inhaled isoflurane. Data were obtained from electronic medical records.SettingICU at large academic medical center where mechanical ventilation was delivered with Draeger Apollo (Draeger Medical, Telford, PA) anesthesia machines.PatientsConsecutive adult patients (≥ 18 yr) with confirmed coronavirus disease 2019 admitted to ICU between April 2, 2020, and May 4, 2020.InterventionsNone.Measurements and main resultsThirty-five mechanically ventilated patients were included in the study, with a mean (sd) age of 59.4 (12.8) years. Twenty-three patients (65.7%) were men. Seventeen patients (48.6%) received standard IV sedation, whereas 18 (51.4%) also received isoflurane. The mean duration of mechanical ventilation (sd) was 23.3 (11.6) days in the standard sedation group and 23.8 (12.5) days in the isoflurane group. Mean (sd) duration of isoflurane exposure was 5.61 (2.99) days, representing 29.1% of total sedation time (sd, 20.4). Cumulative opioid exposure did not differ between the standard sedation and isoflurane sedation groups (mean morphine milligram equivalent 6668 [sd, 1,346] vs 6678 [sd, 2,000] mg). However, the initiation of isoflurane in patients was associated with decreased utilization of propofol (mean daily amount 3,656 [sd, 1,635] before vs 950 [sd, 1,804] mg during isoflurane) and hydromorphone (mean daily amount 48 [sd, 30] before vs 23 [sd, 27] mg).ConclusionsIn the subjects that received isoflurane, its use was associated with significant decreases in propofol and hydromorphone infusions
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Preoperative Plasma Tau-PT217 and Tau-PT181 Are Associated With Postoperative Delirium.
OBJECTIVE: This study aims to identify blood biomarkers of postoperative delirium. BACKGROUND: Phosphorylated tau at threonine 217 (Tau-PT217) and 181 (Tau-PT181) are new Alzheimer disease biomarkers. Postoperative delirium is associated with Alzheimer disease. We assessed associations between Tau-PT217 or Tau-PT181 and postoperative delirium. METHODS: Of 491 patients (65 years old or older) who had a knee replacement, hip replacement, or laminectomy, 139 participants were eligible and included in the analysis. Presence and severity of postoperative delirium were assessed in the patients. Preoperative plasma concentrations of Tau-PT217 and Tau-PT181 were determined by a newly established Nanoneedle technology. RESULTS: Of 139 participants (73±6 years old, 55% female), 18 (13%) developed postoperative delirium. Participants who developed postoperative delirium had higher preoperative plasma concentrations of Tau-PT217 and Tau-PT181 than participants who did not. Preoperative plasma concentrations of Tau-PT217 or Tau-PT181 were independently associated with postoperative delirium after adjusting for age, education, and preoperative Mini-Mental State score [odds ratio (OR) per unit change in the biomarker: 2.05, 95% confidence interval (CI):1.61-2.62, P <0.001 for Tau-PT217; and OR: 4.12; 95% CI: 2.55--6.67, P <0.001 for Tau-PT181]. The areas under the receiver operating curve for predicting delirium were 0.969 (Tau-PT217) and 0.885 (Tau-PT181). The preoperative plasma concentrations of Tau-PT217 or Tau-PT181 were also associated with delirium severity [beta coefficient (β) per unit change in the biomarker: 0.14; 95% CI: 0.09-0.19, P <0.001 for Tau-PT217; and β: 0.41; 95% CI: 0.12-0.70, P =0.006 for Tau-PT181). CONCLUSIONS: Preoperative plasma concentrations of Tau-PT217 and Tau-PT181 were associated with postoperative delirium, with Tau-PT217 being a stronger indicator of postoperative delirium than Tau-PT181
Rationale and design of STAMINA: Senolytics to alleviate mobility issues and neurological impairments in aging, a geroscience feasibility study
The process of cellular senescence is hypothesized to play a critical role in the development of age-related mobility and cognitive impairments, both of which precede the development of Alzheimer's disease. Therefore, senolytic compounds that eliminate senescent cells represent an alternative strategy that may help improve mobility and cognition in older adults; however, clinical trials are lacking. The goal of this paper is to describe the rationale and study design of a 12-week single arm, open label, pre-post pilot study that administers intermittent doses of two senolytic compounds, Dasatinib and quercetin (DQ), in 12 older adults ≥65 years with slow gait speed (<1.0 m/s) and mild cognitive impairment. Eligible participants are asked to take 1250 mg of quercetin and 100 mg of Dasatinib orally once a day for 2 days every 2 weeks, for 6 cycles over 12 consecutive weeks. Both physical and cognitive functional assessments are administered before treatment, as well as 6- and 12- weeks after treatment. Blood and urine samples are taken pre- and post-treatment to assess biomarkers of cellular senescence. The primary outcomes of this trial are feasibility and safety of the intervention, as well as preliminary efficacy on several clinical outcomes (e.g., cerebral blood flow velocity, gait speed, and biomarkers of cellular senescence). The study is approved by the Advarra IRB (#Pro00053594) and a Data Safety Monitoring Board. It is registered at Clinicaltrials.gov (Identifier: NCT05422885).The future results of this study may identify a novel approach for improving mobility and cognition in older adults, thereby preventing progression to Alzheimer's disease