Faculty Bibliography
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58
Longitudinal Lower Airway Microbial Signatures of Acute Cellular Rejection in Lung Transplantation
PMID: 38358857
ISSN: 1535-4970
CID: 5633542
Risk of post-acute sequelae of SARS-CoV-2 infection associated with pre-coronavirus disease obstructive sleep apnea diagnoses: an electronic health record-based analysis from the RECOVER initiative
STUDY OBJECTIVES/OBJECTIVE:Obstructive sleep apnea (OSA) has been associated with more severe acute coronavirus disease-2019 (COVID-19) outcomes. We assessed OSA as a potential risk factor for Post-Acute Sequelae of SARS-CoV-2 (PASC). METHODS:We assessed the impact of preexisting OSA on the risk for probable PASC in adults and children using electronic health record data from multiple research networks. Three research networks within the REsearching COVID to Enhance Recovery initiative (PCORnet Adult, PCORnet Pediatric, and the National COVID Cohort Collaborative [N3C]) employed a harmonized analytic approach to examine the risk of probable PASC in COVID-19-positive patients with and without a diagnosis of OSA prior to pandemic onset. Unadjusted odds ratios (ORs) were calculated as well as ORs adjusted for age group, sex, race/ethnicity, hospitalization status, obesity, and preexisting comorbidities. RESULTS:Across networks, the unadjusted OR for probable PASC associated with a preexisting OSA diagnosis in adults and children ranged from 1.41 to 3.93. Adjusted analyses found an attenuated association that remained significant among adults only. Multiple sensitivity analyses with expanded inclusion criteria and covariates yielded results consistent with the primary analysis. CONCLUSIONS:Adults with preexisting OSA were found to have significantly elevated odds of probable PASC. This finding was consistent across data sources, approaches for identifying COVID-19-positive patients, and definitions of PASC. Patients with OSA may be at elevated risk for PASC after SARS-CoV-2 infection and should be monitored for post-acute sequelae.
PMID: 37166330
ISSN: 1550-9109
CID: 5509392
Optimal dosing of heparin for prophylactic anticoagulation in critically ill COVID-19 patients a systematic review and meta-analysis of randomized controlled trials
PURPOSE/OBJECTIVE:The optimal amount of anticoagulation for critically ill COVID-19 patients is controversial. Therefore, we aimed to evaluate the efficacy and safety of escalated doses of anticoagulation in critically ill patients with severe COVID-19. MATERIALS AND METHODS/METHODS:We conducted a systematic search of three major databases, including PubMed, Cochrane Library, and Embase, from inception to May 2022. Randomized controlled trials (RCTs) were included comparing therapeutic or intermediate doses to standard prophylactic doses of anticoagulants in critically ill COVID-19 patients, with heparins as the only anticoagulation therapy considered. RESULTS:Out of the six RCTs, 2130 patients were administered escalated dose anticoagulation (50.2%) and standard thromboprophylaxis therapy (49.8%). The escalated dose showed no significant impact on mortality (RR, 1.01; 95% CI, 0.90-1.13). Although there was no significant difference in DVT (RR, 0.81; 95% CI, 0.61-1.08), the risk of PE was significantly reduced in patients receiving escalated dose anticoagulation (RR, 0.35; 95% CI, 0.21-0.60), with an increased risk of bleeding events (RR, 1.65; 95% CI, 1.08-2.53). CONCLUSION/CONCLUSIONS:This systematic review and meta-analysis fail to support escalated anticoagulation doses to reduce mortality in critically ill COVID-19 patients. However, higher doses of anticoagulants appear to reduce thrombotic events while increasing the risk of bleeding effectively.
PMCID:10211463
PMID: 37244209
ISSN: 1557-8615
CID: 5508782
Low dose vs high dose tocilizumab in COVID-19 patients with hypoxemic respiratory failure
PURPOSE/OBJECTIVE:Tocilizumab has been shown to decrease mortality when used concomitantly with steroids in COVID-19 with 8 mg/kg (max 800 mg) being the standard dose. Our study sought to assess whether a low dose (400 mg) shows similar benefit compared to a high dose for COVID patients concurrently on the same median dose of steroids. MATERIALS/METHODS/METHODS:A retrospective, multihospital observational study of COVID-19 patients who received tocilizumab in conjunction with steroids between March 2020 and August 2021 was conducted. RESULTS:A total of 407 patients were analyzed with low dose group being significantly more ill at baseline as a higher percentage of patients received vasopressors, were admitted to the ICU and on mechanical ventilation. In the propensity-matched analysis, both groups receiving a median dexamethasone equivalent dose of 10 mg showed no difference in 28-day mortality (p = 0.613). The high dose group had a higher rate of fungal and viral infections. CONCLUSION/CONCLUSIONS:Compared to low dose tocilizumab, the high dose did not provide additional efficacy and mortality benefit but resulted in higher fungal and viral infections. This study illustrates that low dose tocilizumab can be an alternative to high dose during a drug shortage of tocilizumab without compensating for efficacy and safety, conserving resources for more patients.
PMCID:10084735
PMID: 37043893
ISSN: 1557-8615
CID: 5464172
Impact of Time to Intervention on Catheter-Directed Therapy for Pulmonary Embolism
OBJECTIVES: Cather-directed therapies (CDTs) are an evolving therapeutic option for patients with intermediate-risk pulmonary embolism (PE). Although many techniques have been studied, there is limited evidence for the impact of timing of intervention on patient outcomes. Our objective was to assess the association between time to CDT in patients presenting with PE on patient-related outcomes such as length of stay (LOS) and mortality. DESIGN: Retrospective cohort study. SETTING: Single academic center. PATIENTS: We identified patients for which the PE response team had been activated from January 2014 to October 2021. Patients were split into two cohorts depending on whether they went to CDT less than 24 hours from admission (early) versus greater than 24 hours (late). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data on demographics, timing of interventions, pulmonary hemodynamics, and outcomes were collected. Sixty-four patients were included in analysis. Thirty-nine (63.8%) underwent their procedure less than 24 hours from admission, whereas 25 (36.2%) underwent the procedure after 24 hours. The time from admission to CDT was 15.9 hours (9.1-20.3 hr) in the early group versus 33.4 (27.9-41) in the late group (p ≤ 0.001). There was a greater decrease in pulmonary artery systolic pressure after intervention in the early cohort (14 mm Hg [6-20 mm Hg] vs 6 mm Hg [1-10 mm Hg]; p = 0.022). Patients who received earlier intervention were found to have shorter hospital LOS (4 vs 7 d; p = 0.038) and ICU LOS (3 vs 5 d; p = 0.004). There was no difference in inhospital mortality between the groups (17.9% vs 12%; p = 0.523). CONCLUSIONS: Patients who underwent CDT within 24 hours of admission were more likely to have shorter hospital and ICU LOS. The magnitude of change in LOS between the two cohorts was not fully explained by the difference in time to CDT. There were modest improvements in pulmonary hemodynamics in the patients who underwent CDT earlier.
SCOPUS:85147112043
ISSN: 2639-8028
CID: 5424252
LOW-DOSE VERSUS HIGH-DOSE TOCILIZUMAB IN COVID-19 PATIENTS WITH HYPOXIC RESPIRATORY FAILURE [Meeting Abstract]
INTRODUCTION: Tocilizumab has been shown to decrease mortality when used concomitantly with steroids in COVID-19. Tocilizumab dose of 8 mg/kg (max: 800 mg), stemmed from the RECOVERY trial, has been the standard dose for COVID. Due to a drug shortage of tocilizumab, our study seeks to assess whether low dose (400 mg) shows similar benefit compared to high dose for COVID patients concurrently on same median dose of steroids.
METHOD(S): This was a retrospective observational study of COVID-19 patients who received tocilizumab in conjunction with steroids. Between March 2020 and August 2021, adult patients with positive COVID-19 PCR, hypoxic respiratory failure defined as FiO2>70%, and received a dose of tocilizumab in conjunction with steroids were included. Patients were excluded if they have died within 24 hours of treatment initiation. Primary outcome was 28-day mortality and secondary outcomes included biomarker improvement and relative risk of infection. Propensity matched analysis between groups was performed.
RESULT(S): A total of 407 patients met the study criteria and were analyzed. The low dose and high dose tocilizumab group had 222 and 185 patients respectively. Gender and age were similar between groups and all patients received steroids. The low dose group was significantly more ill at baseline as a higher percentage of patients received vasopressors, were admitted to the ICU and on mechanical ventilation. In the propensity-matched analysis of 56 patients in each group, with a median dose of steroid of 10 mg in both groups showed no difference in 28 day mortality (HR 0.82 [95% CI: 0.41-1.67]; p=0.6138). A greater decrease to normalization of CRP (p< 0.0001) and downtrend of ferritin (p=0.503) was observed in the high dose group at day 14. The high dose group trended a higher rate of fungal and viral infections.
CONCLUSION(S): Compared to low dose tocilizumab, high dose did not provide additional efficacy and mortality benefit but resulted in uptrend of fungal and viral infections. While a greater decrease in CRP was seen in the high dose group, it did not translate into lower mortality. This study illustrates that low dose tocilizumab can be an alternative to high dose during a drug shortage of tocilizumab without compensating for efficacy and safety, conserving resources for more patients
METHOD(S): This was a retrospective observational study of COVID-19 patients who received tocilizumab in conjunction with steroids. Between March 2020 and August 2021, adult patients with positive COVID-19 PCR, hypoxic respiratory failure defined as FiO2>70%, and received a dose of tocilizumab in conjunction with steroids were included. Patients were excluded if they have died within 24 hours of treatment initiation. Primary outcome was 28-day mortality and secondary outcomes included biomarker improvement and relative risk of infection. Propensity matched analysis between groups was performed.
RESULT(S): A total of 407 patients met the study criteria and were analyzed. The low dose and high dose tocilizumab group had 222 and 185 patients respectively. Gender and age were similar between groups and all patients received steroids. The low dose group was significantly more ill at baseline as a higher percentage of patients received vasopressors, were admitted to the ICU and on mechanical ventilation. In the propensity-matched analysis of 56 patients in each group, with a median dose of steroid of 10 mg in both groups showed no difference in 28 day mortality (HR 0.82 [95% CI: 0.41-1.67]; p=0.6138). A greater decrease to normalization of CRP (p< 0.0001) and downtrend of ferritin (p=0.503) was observed in the high dose group at day 14. The high dose group trended a higher rate of fungal and viral infections.
CONCLUSION(S): Compared to low dose tocilizumab, high dose did not provide additional efficacy and mortality benefit but resulted in uptrend of fungal and viral infections. While a greater decrease in CRP was seen in the high dose group, it did not translate into lower mortality. This study illustrates that low dose tocilizumab can be an alternative to high dose during a drug shortage of tocilizumab without compensating for efficacy and safety, conserving resources for more patients
EMBASE:640005728
ISSN: 1530-0293
CID: 5513732
Researching COVID to Enhance Recovery (RECOVER) adult study protocol: Rationale, objectives, and design
IMPORTANCE/OBJECTIVE:SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. METHODS:RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. DISCUSSION/CONCLUSIONS:RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options. REGISTRATION/BACKGROUND:NCT05172024.
PMID: 37352211
ISSN: 1932-6203
CID: 5538502
Clinical outcomes and factors associated with pulmonary infarction following acute pulmonary embolism: a retrospective observational study at a US academic centre
OBJECTIVE:Pulmonary infarction is a common clinical and radiographic finding in acute pulmonary embolism (PE), yet the clinical relevance and prognostic significance of pulmonary infarction remain unclear. The study aims to investigate the clinical features, radiographic characteristics, impact of reperfusion therapy and outcomes of patients with pulmonary infarction. DESIGN, SETTING AND PARTICIPANTS:test where appropriate. Multivariate logistic regression was used to evaluate potential risk factors for pulmonary infarction. RESULTS:We identified 143 (29%) cases of pulmonary infarction in 496 patients with PE. Patients with infarction were significantly younger (52±15.9 vs 61±16.6 years, p<0.001) and with fewer comorbidities. Most infarctions occurred in the lower lobes (60%) and involved a single lobe (64%). The presence of right ventricular (RV) strain on CT imaging was significantly more common in patients with infarction (21% vs 14%, p=0.031). There was no significant difference in advanced reperfusion therapy, in-hospital mortality, length of stay and readmissions between groups. In multivariate analysis, age and evidence of RV strain on CT and haemoptysis increased the risk of infarction. CONCLUSIONS:Radiographic evidence of pulmonary infarction was demonstrated in nearly one-third of patients with acute PE. There was no difference in the rate of reperfusion therapies and the presence of infarction did not correlate with poorer outcomes.
PMCID:9806066
PMID: 36581412
ISSN: 2044-6055
CID: 5409722
Reduced CT iodine perfusion score is associated with adverse clinical outcomes in acute pulmonary embolism [Letter]
PMID: 36567600
ISSN: 1477-0377
CID: 5409492
Impact of pulmonary embolism response teams on acute pulmonary embolism: a systematic review and meta-analysis
BACKGROUND:The impact of pulmonary embolism response teams (PERTs) on treatment choice and outcomes of patients with acute pulmonary embolism (PE) is still uncertain. OBJECTIVE:To determine the effect of PERTs in the management and outcomes of patients with PE. METHODS:PubMed, Embase, Web of Science, CINAHL, WorldWideScience and MedRxiv were searched for original articles reporting PERT patient outcomes from 2009. Data were analysed using a random effects model. RESULTS:16 studies comprising 3827 PERT patients and 3967 controls met inclusion criteria. The PERT group had more patients with intermediate and high-risk PE (66.2%) compared to the control group (48.5%). Meta-analysis demonstrated an increased risk of catheter-directed interventions, systemic thrombolysis and surgical embolectomy (odds ratio (OR) 2.10, 95% confidence interval (CI) 1.74-2.53; p<0.01), similar bleeding complications (OR 1.10, 95% CI 0.88-1.37) and decreased utilisation of inferior vena cava (IVC) filters (OR 0.71, 95% CI 0.58-0.88; p<0.01) in the PERT group. Furthermore, there was a nonsignificant trend towards decreased mortality (OR 0.87, 95% CI 0.71-1.07; p=0.19) with PERTs. CONCLUSIONS:The PERT group showed an increased use of advanced therapies and a decreased utilisation of IVC filters. This was not associated with increased bleeding. Despite comprising more severe PE patients, there was a trend towards lower mortality in the PERT group.
PMID: 35831010
ISSN: 1600-0617
CID: 5269262
