- Critical Care Medicine
Clinical Associate Professor, Emergency Medicine
Board Certification: American Board of Internal Medicine, Critical Care Medicine (2015)
Fellowship: University of California - San Francisco (2014) CA
Board Certification: American Board of Emergency Medicine, Emergency Medicine (2013)
Residency: University of California - San Francisco (2012) CA
Medical Education: University of California - San Francisco (2008) CA
MS, University of California-Berkeley, School of Public Health, Health & Medical Sciences (2006)
Current Research and Scholarly Interests
Emergency critical care & resuscitation, ARDS, sepsis
Accelerating COVID-19 Therapeutic Interventions and Vaccines 4 ACUTE
This is a randomized, open label, adaptive platform trial to compare the effectiveness of antithrombotic and additional strategies for prevention of adverse outcomes in COVID-19 positive inpatients
ACTIV-3: Therapeutics for Inpatients With COVID-19
This study looks at the safety and effectiveness of different drugs in treating COVID-19 in people who have been hospitalized with the infection. Participants in the study will be treated with either a study drug plus current standard of care (SOC), or with placebo plus current SOC.
ARrest RESpiraTory Failure From PNEUMONIA
This research study seeks to establish the effectiveness of a combination of an inhaled corticosteroid and a beta agonist compared to placebo for the prevention of acute respiratory failure (ARF) in hospitalized patients with pneumonia and hypoxemia.
Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis
Multicenter, prospective, phase 3 randomized non-blinded interventional trial of fluid treatment strategies in the first 24 hours for patients with sepsis-induced hypotension. The aim of the study is to determine the impact of a restrictive fluids strategy (vasopressors first followed by rescue fluids) as compared to a liberal fluid strategy (fluids first followed by rescue vasopressors) on 90-day in-hospital mortality in patients with sepsis-induced hypotension.
Emergency Critical Care Intervention Study, Stanford University
We are studying the effects of ICU-trained RNs and MDs on outcomes for critically ill patients in the Emergency Department.
Stanford University Hospital
Stanford ICU Biobank
Graduate and Fellowship Programs
Critical Care Medicine (Fellowship Program)
Association Between mRNA Vaccination and COVID-19 Hospitalization and Disease Severity.
Importance: A comprehensive understanding of the benefits of COVID-19 vaccination requires consideration of disease attenuation, determined as whether people who develop COVID-19 despite vaccination have lower disease severity than unvaccinated people.Objective: To evaluate the association between vaccination with mRNA COVID-19 vaccines-mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech)-and COVID-19 hospitalization, and, among patients hospitalized with COVID-19, the association with progression to critical disease.Design, Setting, and Participants: A US 21-site case-control analysis of 4513 adults hospitalized between March 11 and August 15, 2021, with 28-day outcome data on death and mechanical ventilation available for patients enrolled through July 14, 2021. Date of final follow-up was August 8, 2021.Exposures: COVID-19 vaccination.Main Outcomes and Measures: Associations were evaluated between prior vaccination and (1) hospitalization for COVID-19, in which case patients were those hospitalized for COVID-19 and control patients were those hospitalized for an alternative diagnosis; and (2) disease progression among patients hospitalized for COVID-19, in which cases and controls were COVID-19 patients with and without progression to death or mechanical ventilation, respectively. Associations were measured with multivariable logistic regression.Results: Among 4513 patients (median age, 59 years [IQR, 45-69]; 2202 [48.8%] women; 23.0% non-Hispanic Black individuals, 15.9% Hispanic individuals, and 20.1% with an immunocompromising condition), 1983 were case patients with COVID-19 and 2530 were controls without COVID-19. Unvaccinated patients accounted for 84.2% (1669/1983) of COVID-19 hospitalizations. Hospitalization for COVID-19 was significantly associated with decreased likelihood of vaccination (cases, 15.8%; controls, 54.8%; adjusted OR, 0.15; 95% CI, 0.13-0.18), including for sequenced SARS-CoV-2 Alpha (8.7% vs 51.7%; aOR, 0.10; 95% CI, 0.06-0.16) and Delta variants (21.9% vs 61.8%; aOR, 0.14; 95% CI, 0.10-0.21). This association was stronger for immunocompetent patients (11.2% vs 53.5%; aOR, 0.10; 95% CI, 0.09-0.13) than immunocompromised patients (40.1% vs 58.8%; aOR, 0.49; 95% CI, 0.35-0.69) (P<.001) and weaker at more than 120 days since vaccination with BNT162b2 (5.8% vs 11.5%; aOR, 0.36; 95% CI, 0.27-0.49) than with mRNA-1273 (1.9% vs 8.3%; aOR, 0.15; 95% CI, 0.09-0.23) (P<.001). Among 1197 patients hospitalized with COVID-19, death or invasive mechanical ventilation by day 28 was associated with decreased likelihood of vaccination (12.0% vs 24.7%; aOR, 0.33; 95% CI, 0.19-0.58).Conclusions and Relevance: Vaccination with an mRNA COVID-19 vaccine was significantly less likely among patients with COVID-19 hospitalization and disease progression to death or mechanical ventilation. These findings are consistent with risk reduction among vaccine breakthrough infections compared with absence of vaccination.
View details for DOI 10.1001/jama.2021.19499
View details for PubMedID 34734975
Comparative Effectiveness of Moderna, Pfizer-BioNTech, and Janssen (Johnson & Johnson) Vaccines in Preventing COVID-19 Hospitalizations Among Adults Without Immunocompromising Conditions - United States, March-August 2021
MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT
2021; 70 (38): 1337-1343
Three COVID-19 vaccines are authorized or approved for use among adults in the United States (1,2). Two 2-dose mRNA vaccines, mRNA-1273 from Moderna and BNT162b2 from Pfizer-BioNTech, received Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) in December 2020 for persons aged ≥18 years and aged ≥16 years, respectively. A 1-dose viral vector vaccine (Ad26.COV2 from Janssen [Johnson & Johnson]) received EUA in February 2021 for persons aged ≥18 years (3). The Pfizer-BioNTech vaccine received FDA approval for persons aged ≥16 years on August 23, 2021 (4). Current guidelines from FDA and CDC recommend vaccination of eligible persons with one of these three products, without preference for any specific vaccine (4,5). To assess vaccine effectiveness (VE) of these three products in preventing COVID-19 hospitalization, CDC and collaborators conducted a case-control analysis among 3,689 adults aged ≥18 years who were hospitalized at 21 U.S. hospitals across 18 states during March 11-August 15, 2021. An additional analysis compared serum antibody levels (anti-spike immunoglobulin G [IgG] and anti-receptor binding domain [RBD] IgG) to SARS-CoV-2, the virus that causes COVID-19, among 100 healthy volunteers enrolled at three hospitals 2-6 weeks after full vaccination with the Moderna, Pfizer-BioNTech, or Janssen COVID-19 vaccine. Patients with immunocompromising conditions were excluded. VE against COVID-19 hospitalizations was higher for the Moderna vaccine (93%; 95% confidence interval [CI] = 91%-95%) than for the Pfizer-BioNTech vaccine (88%; 95% CI = 85%-91%) (p = 0.011); VE for both mRNA vaccines was higher than that for the Janssen vaccine (71%; 95% CI = 56%-81%) (all p<0.001). Protection for the Pfizer-BioNTech vaccine declined 4 months after vaccination. Postvaccination anti-spike IgG and anti-RBD IgG levels were significantly lower in persons vaccinated with the Janssen vaccine than the Moderna or Pfizer-BioNTech vaccines. Although these real-world data suggest some variation in levels of protection by vaccine, all FDA-approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization.
View details for Web of Science ID 000701940200005
View details for PubMedID 34555004
View details for PubMedCentralID PMC8459899
Sustained Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Associated Hospitalizations Among Adults - United States, March-July 2021
MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT
2021; 70 (34): 1156-1162
Real-world evaluations have demonstrated high effectiveness of vaccines against COVID-19-associated hospitalizations (1-4) measured shortly after vaccination; longer follow-up is needed to assess durability of protection. In an evaluation at 21 hospitals in 18 states, the duration of mRNA vaccine (Pfizer-BioNTech or Moderna) effectiveness (VE) against COVID-19-associated hospitalizations was assessed among adults aged ≥18 years. Among 3,089 hospitalized adults (including 1,194 COVID-19 case-patients and 1,895 non-COVID-19 control-patients), the median age was 59 years, 48.7% were female, and 21.1% had an immunocompromising condition. Overall, 141 (11.8%) case-patients and 988 (52.1%) controls were fully vaccinated (defined as receipt of the second dose of Pfizer-BioNTech or Moderna mRNA COVID-19 vaccines ≥14 days before illness onset), with a median interval of 65 days (range = 14-166 days) after receipt of second dose. VE against COVID-19-associated hospitalization during the full surveillance period was 86% (95% confidence interval [CI] = 82%-88%) overall and 90% (95% CI = 87%-92%) among adults without immunocompromising conditions. VE against COVID-19- associated hospitalization was 86% (95% CI = 82%-90%) 2-12 weeks and 84% (95% CI = 77%-90%) 13-24 weeks from receipt of the second vaccine dose, with no significant change between these periods (p = 0.854). Whole genome sequencing of 454 case-patient specimens found that 242 (53.3%) belonged to the B.1.1.7 (Alpha) lineage and 74 (16.3%) to the B.1.617.2 (Delta) lineage. Effectiveness of mRNA vaccines against COVID-19-associated hospitalization was sustained over a 24-week period, including among groups at higher risk for severe COVID-19; ongoing monitoring is needed as new SARS-CoV-2 variants emerge. To reduce their risk for hospitalization, all eligible persons should be offered COVID-19 vaccination.
View details for Web of Science ID 000691315200005
View details for PubMedID 34437524
Tracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS.
2021; 12 (1): 5152
The immunological features that distinguish COVID-19-associated acute respiratory distress syndrome (ARDS) from other causes of ARDS are incompletely understood. Here, we report the results of comparative lower respiratory tract transcriptional profiling of tracheal aspirate from 52 critically ill patients with ARDS from COVID-19 or from other etiologies, as well as controls without ARDS. In contrast to a "cytokine storm," we observe reduced proinflammatory gene expression in COVID-19 ARDS when compared to ARDS due to other causes. COVID-19 ARDS is characterized by a dysregulated host response with increased PTEN signaling and elevated expression of genes with non-canonical roles in inflammation and immunity. In silico analysis of gene expression identifies several candidate drugs that may modulate gene expression in COVID-19 ARDS, including dexamethasone and granulocyte colony stimulating factor. Compared to ARDS due to other types of viral pneumonia, COVID-19 is characterized by impaired interferon-stimulated gene (ISG) expression. The relationship between SARS-CoV-2 viral load and expression of ISGs is decoupled in patients with COVID-19 ARDS when compared to patients with mild COVID-19. In summary, assessment of host gene expression in the lower airways of patients reveals distinct immunological features of COVID-19 ARDS.
View details for DOI 10.1038/s41467-021-25040-5
View details for PubMedID 34446707
Effectiveness of SARS-CoV-2 mRNA Vaccines for Preventing Covid-19 Hospitalizations in the United States.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
BACKGROUND: As SARS-CoV-2 vaccination coverage increases in the United States (US), there is a need to understand the real-world effectiveness against severe Covid-19 and among people at increased risk for poor outcomes.METHODS: In a multicenter case-control analysis of US adults hospitalized March 11-May 5, 2021, we evaluated vaccine effectiveness to prevent Covid-19 hospitalizations by comparing odds of prior vaccination with an mRNA vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with Covid-19 and hospital-based controls who tested negative for SARS-CoV-2.RESULTS: Among 1212 participants, including 593 cases and 619 controls, median age was 58 years, 22.8% were Black, 13.9% were Hispanic, and 21.0% had immunosuppression. SARS-CoV-2 lineage B.1.1.7 (Alpha) was the most common variant (67.9% of viruses with lineage determined). Full vaccination (receipt of two vaccine doses ≥14 days before illness onset) had been received by 8.2% of cases and 36.4% of controls. Overall vaccine effectiveness was 87.1% (95% CI: 80.7 to 91.3%). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18-49 years (97.4%; 95% CI: 79.3 to 99.7%). Among 45 patients with vaccine-breakthrough Covid hospitalizations, 44 (97.8%) were ≥50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (62.9%; 95% CI: 20.8 to 82.6%) than without immunosuppression (91.3%; 95% CI: 85.6 to 94.8%).CONCLUSION: During March-May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing Covid-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population.
View details for DOI 10.1093/cid/ciab687
View details for PubMedID 34358310
Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19.
The New England journal of medicine
BACKGROUND: Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19.METHODS: In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge.RESULTS: The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis.CONCLUSIONS: In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis. (REMAP-CAP, ACTIV-4a, and ATTACC ClinicalTrials.gov numbers, NCT02735707, NCT04505774, NCT04359277, and NCT04372589.).
View details for DOI 10.1056/NEJMoa2103417
View details for PubMedID 34351722
Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19.
The New England journal of medicine
BACKGROUND: Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19.METHODS: In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level.RESULTS: The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis.CONCLUSIONS: In noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589, NCT04505774, NCT02735707, and NCT04359277.).
View details for DOI 10.1056/NEJMoa2105911
View details for PubMedID 34351721
Prospective validation of an 11-gene mRNA host response score for mortality risk stratification in the intensive care unit.
2021; 11 (1): 13062
Several clinical calculators predict intensive care unit (ICU) mortality, however these are cumbersome and often require 24h of data to calculate. Retrospective studies have demonstrated the utility of whole blood transcriptomic analysis in predicting mortality. In this study, we tested prospective validation of an 11-gene messenger RNA (mRNA) score in an ICU population. Whole blood mRNA from 70 subjects in the Stanford ICU Biobank with samples collected within 24h of Emergency Department presentation were used to calculate an 11-gene mRNA score. We found that the 11-gene score was highly associated with 60-day mortality, with an area under the receiver operating characteristic curve of 0.68 in all patients, 0.77 in shock patients, and 0.98 in patients whose primary determinant of prognosis was acute illness. Subjects with the highest quartile of mRNA scores were more likely to die in hospital (40% vs 7%, p<0.01) and within 60days (40% vs 15%, p=0.06). The 11-gene score improved prognostication with a categorical Net Reclassification Improvement index of 0.37 (p=0.03) and an Integrated Discrimination Improvement index of 0.07 (p=0.02) when combined with Simplified Acute Physiology Score 3 or Acute Physiology and Chronic Health Evaluation II score. The test performed poorly in the 95 independent samples collected>24h after emergency department presentation. Tests will target a 30-min turnaround time, allowing for rapid results early in admission. Moving forward, this test may provide valuable real-time prognostic information to improve triage decisions and allow for enrichment of clinical trials.
View details for DOI 10.1038/s41598-021-91201-7
View details for PubMedID 34158514
Adults Hospitalized with COVID-19 -United States, March-June and October-December 2020: Implications for the Potential Effects of COVID-19 Tier-1 Vaccination on Future Hospitalizations and Outcomes.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
BACKGROUND: Because of the increased risk for severe coronavirus disease 2019 (COVID-19), the Advisory Committee on Immunization Practices (ACIP) initially prioritized COVID-19 vaccination for persons in long-term care facilities (LTCF), persons aged ≥65 years, and persons aged 16-64 years with high-risk medical conditions when there is limited vaccine supply. We compared characteristics and severe outcomes of hospitalized patients with COVID-19 in the United States between early and later in the pandemic categorized by groups at higher risk of severe COVID-19.METHODS: Observational study of sampled patients aged ≥18 years who tested positive for SARS-CoV-2 and admitted to one of 14 academic hospitals in the United States during March-June and October-December 2020. Demographic and clinical information were gathered from electronic health record data.RESULTS: Among 647 patients, 91% met ≥1 of the following risk factors for severe COVID-19 [91% March-June (n=434); 90% October-December (n=213)]; 19% were LTCF residents, 45% were aged ≥65-years, and 84% had ≥1 high-risk condition. The proportion of patients who resided in a LTCF declined significantly (25% vs. 6%) from early to later pandemic periods. Compared with patients at lower risk for severe COVID-19, in-hospital mortality was higher among patients at high risk for severe COVID-19 (20% vs. 7%); these differences were consistently observed between March-June and October-December.CONCLUSIONS: Most adults hospitalized with COVID-19 were those recommended to be prioritized for vaccination based on risk for developing severe COVID-19. These findings highlight the urgency to vaccinate patients at high risk for severe COVID-19 and monitor vaccination impact on hospitalizations and outcomes.
View details for DOI 10.1093/cid/ciab319
View details for PubMedID 33977301
Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Among Hospitalized Adults Aged >= 65 Years - United States, January-March 2021
MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT
2021; 70 (18): 674–79
Adults aged ≥65 years are at increased risk for severe outcomes from COVID-19 and were identified as a priority group to receive the first COVID-19 vaccines approved for use under an Emergency Use Authorization (EUA) in the United States (1-3). In an evaluation at 24 hospitals in 14 states,* the effectiveness of partial or full vaccination† with Pfizer-BioNTech or Moderna vaccines against COVID-19-associated hospitalization was assessed among adults aged ≥65 years. Among 417 hospitalized adults aged ≥65 years (including 187 case-patients and 230 controls), the median age was 73 years, 48% were female, 73% were non-Hispanic White, 17% were non-Hispanic Black, 6% were Hispanic, and 4% lived in a long-term care facility. Adjusted vaccine effectiveness (VE) against COVID-19-associated hospitalization among adults aged ≥65 years was estimated to be 94% (95% confidence interval [CI] = 49%-99%) for full vaccination and 64% (95% CI = 28%-82%) for partial vaccination. These findings are consistent with efficacy determined from clinical trials in the subgroup of adults aged ≥65 years (4,5). This multisite U.S. evaluation under real-world conditions suggests that vaccination provided protection against COVID-19-associated hospitalization among adults aged ≥65 years. Vaccination is a critical tool for reducing severe COVID-19 in groups at high risk.
View details for Web of Science ID 000647643800003
View details for PubMedID 33956782
Symptoms and recovery among adult outpatients with and without COVID-19 at 11 healthcare facilities-July 2020, United States.
Influenza and other respiratory viruses
BACKGROUND: Symptoms of mild COVID-19 illness are non-specific and may persist for prolonged periods. Effects on quality of life of persistent poor physical or mental health associated with COVID-19 are not well understood.METHODS: Adults aged ≥18years with laboratory-confirmed COVID-19 and matched control patients who tested negative for SARS-CoV-2 infection at outpatient facilities associated with 11 medical centers in the United States were interviewed to assess symptoms, illness duration, and health-related quality of life. Duration of symptoms, health-related quality of life measures, and days of poor physical health by symptoms experienced during illness were compared between case patients and controls using Wilcoxon rank-sum tests. Symptoms associated with COVID-19 case status were evaluated by multivariable logistic regression.RESULTS: Among 320 participants included, 157 were COVID-19 cases and 163 were SARS-CoV-2 negative controls. Loss of taste or smell was reported by 63% of cases and 6% of controls and was strongly associated with COVID-19 in logistic regression models (adjusted odds ratio [aOR]=32.4; 95% confidence interval [CI], 12.6-83.1). COVID-19 cases were more likely than controls to have experienced fever, body aches, weakness, or fatigue during illness, and to report ≥1 persistent symptom more than 14days after symptom onset (50% vs 32%, P<.001). Cases reported significantly more days of poor physical health during the past 14days than controls (P<.01).CONCLUSIONS: Differentiating COVID-19 from other acute illnesses will require widespread diagnostic testing, especially during influenza seasons. Persistent COVID-19-related symptoms may negatively affect quality of life, even among those initially presenting with mild illness.
View details for DOI 10.1111/irv.12832
View details for PubMedID 33405338
ICU Bed Utilization During the Coronavirus Disease 2019 Pandemic in a Multistate Analysis-March to June 2020.
Critical care explorations
2021; 3 (3): e0361
Given finite ICU bed capacity, knowledge of ICU bed utilization during the coronavirus disease 2019 pandemic is critical to ensure future strategies for resource allocation and utilization. We sought to examine ICU census trends in relation to ICU bed capacity during the rapid increase in severe coronavirus disease 2019 cases early during the pandemic.Observational cohort study.Thirteen geographically dispersed academic medical centers in the United States.We obtained daily ICU censuses from March 26 to June 30, 2020, as well as prepandemic ICU bed capacities. The primary outcome was daily census of ICU patients stratified by coronavirus disease 2019 and mechanical ventilation status in relation to ICU capacity.None.Prepandemic overall ICU capacity ranged from 62 to 225 beds (median 109). During the study period, the median daily coronavirus disease 2019 ICU census per hospital ranged from 1 to 84 patients, and the daily ICU census exceeded overall ICU capacity for at least 1 day at five institutions. The number of critically ill patients exceeded ICU capacity for a median (interquartile range) of 17 (12-50) of 97 days at these five sites. All 13 institutions experienced decreases in their noncoronavirus disease ICU population, whereas local coronavirus disease 2019 cases increased. Coronavirus disease 2019 patients reached their greatest proportion of ICU capacity on April 12, 2020, when they accounted for 44% of ICU patients across all participating hospitals. Maximum ICU census ranged from 52% to 289% of overall ICU capacity, with three sites less than 80%, four sites 80-100%, five sites 100-128%, and one site 289%.From March to June 2020, the coronavirus disease 2019 pandemic led to ICU censuses greater than ICU bed capacity at fives of 13 institutions evaluated. These findings demonstrate the short-term adaptability of U.S. healthcare institutions in redirecting limited resources to accommodate a public health emergency.
View details for DOI 10.1097/CCE.0000000000000361
View details for PubMedID 33786437
View details for PubMedCentralID PMC7994039
Effectiveness of SARS-CoV-2 mRNA Vaccines for Preventing Covid-19 Hospitalizations in the United States.
medRxiv : the preprint server for health sciences
As SARS-CoV-2 vaccination coverage increases in the United States (US), there is a need to understand the real-world effectiveness against severe Covid-19 and among people at increased risk for poor outcomes.In a multicenter case-control analysis of US adults hospitalized March 11 - May 5, 2021, we evaluated vaccine effectiveness to prevent Covid-19 hospitalizations by comparing odds of prior vaccination with an mRNA vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with Covid-19 and hospital-based controls who tested negative for SARS-CoV-2.Among 1210 participants, median age was 58 years, 22.8% were Black, 13.8% were Hispanic, and 20.6% had immunosuppression. SARS-CoV-2 lineage B.1.1.7 was most common variant (59.7% of sequenced viruses). Full vaccination (receipt of two vaccine doses ≥14 days before illness onset) had been received by 45/590 (7.6%) cases and 215/620 (34.7%) controls. Overall vaccine effectiveness was 86.9% (95% CI: 80.4 to 91.2%). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18-49 years (97.3%; 95% CI: 78.9 to 99.7%). Among 45 patients with vaccine-breakthrough Covid hospitalizations, 44 (97.8%) were ≥50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (59.2%; 95% CI: 11.9 to 81.1%) than without immunosuppression (91.3%; 95% CI: 85.5 to 94.7%).During March-May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing Covid-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population.
View details for DOI 10.1101/2021.07.08.21259776
View details for PubMedID 34268515
View details for PubMedCentralID PMC8282104
Point-of-Care Lung Ultrasound Pattern in Healthy Parturients: Prevalence of Pulmonary Interstitial Syndrome Following Vaginal Delivery, Elective and Unplanned Intrapartum Cesarean Delivery.
Anesthesia and analgesia
Pregnancy-related cardiovascular physiologic changes increase the likelihood of pulmonary edema, with the risk of fluid extravasating into the pulmonary interstitium being potentially at a maximum during the early postpartum period. Data on the impact of labor and peripartum hemodynamic strain on lung ultrasound (LUS) are limited, and the prevalence of subclinical pulmonary interstitial syndrome in peripartum women is poorly described. The primary aim of this exploratory study was to estimate the prevalence of pulmonary interstitial syndrome in healthy term parturients undergoing vaginal (VD), elective (eCD), and unplanned intrapartum cesarean deliveries (uCD). Secondary aims were to estimate the prevalence of positive lung regions (≥3 B-lines on LUS per region) and to assess the associations between positive lung regions and possible contributing factors.In this prospective observational cohort study, healthy women at term undergoing VD, eCD, or uCD were enrolled. Following international consensus recommendations, a LUS examination was performed within 4 hours after delivery applying an 8-region technique. Pulmonary interstitial syndrome was defined by the presence of 2 or more positive lung regions per hemithorax. Ultrasound studies were reviewed by 2 blinded reviewers and assessed for interobserver reliability.Seventy-five women were assessed (n = 25 per group). No pulmonary interstitial syndrome was found in the VD and eCD groups (each 0 of 25; 0%, 95% confidence interval [CI], 0-13.7). Pulmonary interstitial syndrome was found in 2 of 25 (8%, 95% CI, 1-26) women undergoing an uCD (P = .490 for VD versus uCD and P = .490 for eCD versus uCD). In 1 woman, this correlated clinically with the development of pulmonary edema. One or more positive lung regions were present in 5 of 25 (20%), 6 of 25 (24%), and 11 of 25 (44%) parturients following VD, eCD, and uCD, respectively (P = .136). Positive lung regions were predominantly found in lateral lung regions. The number of positive lung regions showed a weak correlation with patient age (r = 0.25, 95% CI, 0.05-0.47; P = .033). No significant association was found between LUS pattern and parity, duration of labor, labor augmentation, labor induction, estimated total intravenous fluid intake, or net intravenous fluid intake.Although many focal areas of increased extravascular lung water (20%-44% prevalence) can be identified on LUS, the overall prevalence of pulmonary interstitial syndrome was 2.7% (2 of 75; 95% CI, 0.3-9.3) among healthy term parturients soon after delivery. Focal areas of positive lung water regions were weakly correlated with maternal age.
View details for DOI 10.1213/ANE.0000000000005464
View details for PubMedID 33721873
COVID-19 ARDS is characterized by a dysregulated host response that differs from cytokine storm and is modified by dexamethasone.
We performed comparative lower respiratory tract transcriptional profiling of 52 critically ill patients with the acute respiratory distress syndrome (ARDS) from COVID-19 or from other etiologies, as well as controls without ARDS. In contrast to a cytokine storm, we observed reduced proinflammatory gene expression in COVID-19 ARDS when compared to ARDS due to other causes. COVID-19 ARDS was characterized by a dysregulated host response with increased PTEN signaling and elevated expression of genes with non-canonical roles in inflammation and immunity that were predicted to be modulated by dexamethasone and granulocyte colony stimulating factor. Compared to ARDS due to other types of viral pneumonia, COVID-19 was characterized by impaired interferon-stimulated gene expression (ISG). We found that the relationship between SARS-CoV-2 viral load and expression of ISGs was decoupled in patients with COVID-19 ARDS when compared to patients with mild COVID-19. In summary, assessment of host gene expression in the lower airways of patients with COVID-19 ARDS did not demonstrate cytokine storm but instead revealed a unique and dysregulated host response predicted to be modified by dexamethasone.
View details for DOI 10.21203/rs.3.rs-141578/v1
View details for PubMedID 33469573
View details for PubMedCentralID PMC7814832
Effect of emergency critical care nurses and emergency department boarding time on in-hospital mortality in critically ill patients.
The American journal of emergency medicine
2020; 41: 120–24
STUDY HYPOTHESIS: We hypothesized that establishing a program of specialized emergency critical care (ECC) nurses in the ED would improve mortality of ICU patients boarding in the ED.METHODS: This was a retrospective before-after cohort study using electronic health record data at an academic medical center. We compared in-hospital mortality between the pre- and post-intervention periods and between non-prolonged (≤6h) boarding time and prolonged (>6h) boarding time. In-hospital mortality was stratified by illness severity (eccSOFA category) and adjusted using logistic regression.RESULTS: Severity-adjusted in-hospital mortality decreased from 12.8% pre-intervention to 12.3% post-intervention (-0.5% (95% CI, -3.1% to 2.1%), which was not statistically significant. This was despite a concurrent increase in ED and hospital crowding. The proportion of ECC patients downgraded to a lower level of care while still in the ED increased from 6.4% in the pre-intervention period to 17.0% in the post-intervention period. (+10.6%, 8.2% to 13.0%, p<0.001). Severity-adjusted mortality was 12.8% in the non-prolonged group vs. 11.3% in the prolonged group (p=0.331).CONCLUSIONS: During the post-intervention period, there was a significant increase in illness severity, hospital congestion, ED boarding time, and downgrades in the ED, but no significant change in mortality. These findings suggest that ECC nurses may improve the safety of boarding ICU patients in the ED. Longer ED boarding times were not associated with higher mortality in either the pre- or post-intervention periods.
View details for DOI 10.1016/j.ajem.2020.12.067
View details for PubMedID 33421675
Community and Close Contact Exposures Associated with COVID-19 Among Symptomatic Adults >= 18Years in 11 Outpatient Health Care Facilities - United States, July 2020
MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT
2020; 69 (36): 1258–64
Community and close contact exposures continue to drive the coronavirus disease 2019 (COVID-19) pandemic. CDC and other public health authorities recommend community mitigation strategies to reduce transmission of SARS-CoV-2, the virus that causes COVID-19 (1,2). Characterization of community exposures can be difficult to assess when widespread transmission is occurring, especially from asymptomatic persons within inherently interconnected communities. Potential exposures, such as close contact with a person with confirmed COVID-19, have primarily been assessed among COVID-19 cases, without a non-COVID-19 comparison group (3,4). To assess community and close contact exposures associated with COVID-19, exposures reported by case-patients (154) were compared with exposures reported by control-participants (160). Case-patients were symptomatic adults (persons aged ≥18 years) with SARS-CoV-2 infection confirmed by reverse transcription-polymerase chain reaction (RT-PCR) testing. Control-participants were symptomatic outpatient adults from the same health care facilities who had negative SARS-CoV-2 test results. Close contact with a person with known COVID-19 was more commonly reported among case-patients (42%) than among control-participants (14%). Case-patients were more likely to have reported dining at a restaurant (any area designated by the restaurant, including indoor, patio, and outdoor seating) in the 2 weeks preceding illness onset than were control-participants (adjusted odds ratio [aOR] = 2.4; 95% confidence interval [CI] = 1.5-3.8). Restricting the analysis to participants without known close contact with a person with confirmed COVID-19, case-patients were more likely to report dining at a restaurant (aOR = 2.8, 95% CI = 1.9-4.3) or going to a bar/coffee shop (aOR = 3.9, 95% CI = 1.5-10.1) than were control-participants. Exposures and activities where mask use and social distancing are difficult to maintain, including going to places that offer on-site eating or drinking, might be important risk factors for acquiring COVID-19. As communities reopen, efforts to reduce possible exposures at locations that offer on-site eating and drinking options should be considered to protect customers, employees, and communities.
View details for Web of Science ID 000568709500005
View details for PubMedID 32915165
View details for PubMedCentralID PMC7499837
Cytokine profile in plasma of severe COVID-19 does not differ from ARDS and sepsis.
BACKGROUND: Elevated levels of inflammatory cytokines have been associated with poor outcomes among COVID-19 patients. It is unknown, however, how these levels compare to those observed in critically ill patients with ARDS or sepsis due to other causes.METHODS: We used a luminex assay to determine expression of 76 cytokines from plasma of hospitalized COVID-19 patients and banked plasma samples from ARDS and sepsis patients. Our analysis focused on detecting statistical differences in levels of 6 cytokines associated with cytokine storm (IL-1b, IL-1RA, IL-6, IL-8, IL-18, and TNFalpha) between patients with moderate COVID-19, severe COVID-19, and ARDS or sepsis.RESULTS: 15 hospitalized COVID-19 patients, 9 of whom were critically ill, were compared to critically ill patients with ARDS (n = 12) or sepsis (n = 16). There were no statistically significant differences in baseline levels of IL-1b, IL-1RA, IL-6, IL-8, IL-18, and TNFalpha between patients with COVID-19 and critically ill controls with ARDS or sepsis.CONCLUSIONS: Levels of inflammatory cytokines were not higher in severe COVID-19 patients than in moderate COVID-19 or critically ill patients with ARDS or sepsis in this small cohort. Broad use of immunosuppressive therapies in ARDS has failed in numerous Phase 3 studies; use of these therapies in unselected patients with COVID-19 may be unwarranted.FUNDING: A.J.R.: Stanford ICU Biobank NHLBI K23 HL125663. C.A.B.: Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Diseases #1016687; NIH/NIAID U19AI057229-16 (PI MM Davis); Stanford Maternal Child Health Research Institute; Chan Zuckerberg Biohub.
View details for DOI 10.1172/jci.insight.140289
View details for PubMedID 32706339
Characteristics of Adult Outpatients and Inpatients with COVID-19-11 Academic Medical Centers, United States, March-May 2020
MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT
2020; 69 (26): 841–46
Descriptions of coronavirus disease 2019 (COVID-19) in the United States have focused primarily on hospitalized patients. Reports documenting exposures to SARS-CoV-2, the virus that causes COVID-19, have generally been described within congregate settings, such as meat and poultry processing plants (1) and long-term care facilities (2). Understanding individual behaviors and demographic characteristics of patients with COVID-19 and risks for severe illness requiring hospitalization can inform efforts to reduce transmission. During April 15-May 24, 2020, telephone interviews were conducted with a random sample of adults aged ≥18 years who had positive reverse transcription-polymerase chain reaction (RT-PCR) test results for SARS-CoV-2 in outpatient and inpatient settings at 11 U.S. academic medical centers in nine states. Respondents were contacted 14-21 days after SARS-CoV-2 testing and asked about their demographic characteristics, underlying chronic conditions, symptoms experienced on the date of testing, and potential exposures to SARS-CoV-2 during the 2 weeks before illness onset (or the date of testing among those who did not report symptoms at the time of testing). Among 350 interviewed patients (271 [77%] outpatients and 79 [23%] inpatients), inpatients were older, more likely to be Hispanic and to report dyspnea than outpatients. Fewer inpatients (39%, 20 of 51) reported a return to baseline level of health at 14-21 days than did outpatients (64%, 150 of 233) (p = 0.001). Overall, approximately one half (46%) of patients reported known close contact with someone with COVID-19 during the preceding 2 weeks. This was most commonly a family member (45%) or a work colleague (34%). Approximately two thirds (64%, 212 of 333) of participants were employed; only 35 of 209 (17%) were able to telework. These findings highlight the need for screening, case investigation, contact tracing, and isolation of infected persons to control transmission of SARS-CoV-2 infection during periods of community transmission. The need for enhanced measures to ensure workplace safety, including ensuring social distancing and more widespread use of cloth face coverings, are warranted (3).
View details for Web of Science ID 000545314500007
View details for PubMedID 32614810
View details for PubMedCentralID PMC7332092
ARDS Subphenotypes: Understanding a Heterogeneous Syndrome.
Critical care (London, England)
2020; 24 (1): 102
This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2020. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2020. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.
View details for DOI 10.1186/s13054-020-2778-x
View details for PubMedID 32204722
eccSOFA: SOFA illness severity score adapted to predict in-hospital mortality in emergency critical care patients.
The American journal of emergency medicine
2020; 41: 145–51
Boarding of ICU patients in the ED is increasing. Illness severity scores may help emergency physicians stratify risk to guide earlier transfer to the ICU and assess pre-ICU interventions by adjusting for baseline mortality risk. Most existing illness severity scores are based on data that is not available at the time of the hospital admission decision or cannot be extracted from the electronic health record (EHR). We adapted the SOFA score to create a new illness severity score (eccSOFA) that can be calculated at the time of ICU admission order entry in the ED using EHR data. We evaluated this score in a cohort of emergency critical care (ECC) patients at a single academic center over a period of 3 years.This was a retrospective cohort study using EHR data to assess predictive accuracy of eccSOFA for estimating in-hospital mortality risk. The patient population included all adult patients who had a critical care admission order entered while in the ED of an academic medical center between 10/24/2013 and 9/30/2016. eccSOFA's discriminatory ability for in-hospital mortality was assessed using ROC curves.Of the 3912 patients whose in-hospital mortality risk was estimated, 2260 (57.8%) were in the low-risk group (scores 0-3), 1203 (30.8%) in the intermediate-risk group (scores 4-7), and 449 (11.5%) in the high-risk group (scores 8+). In-hospital mortality for the low-, intermediate, and high-risk groups was 4.2% (95%CI: 3.4-5.1), 15.5% (95% CI 13.5-17.6), and 37.9% (95% CI 33.4-42.3) respectively. The AUROC was 0.78 (95%CI: 0.75-0.80) for the integer score and 0.75 (95% CI: 0.72-0.77) for the categorical eccSOFA.As a predictor of in-hospital mortality, eccSOFA can be calculated based on variables that are commonly available at the time of critical care admission order entry in the ED and has discriminatory ability that is comparable to other commonly used illness severity scores. Future studies should assess the calibration of our absolute risk predictions.
View details for DOI 10.1016/j.ajem.2020.12.018
View details for PubMedID 33453549
Telework Before Illness Onset Among Symptomatic Adults Aged ≥18 Years With and Without COVID-19 in 11 Outpatient Health Care Facilities - United States, July 2020.
MMWR. Morbidity and mortality weekly report
2020; 69 (44): 1648–53
Since March 2020, large-scale efforts to reduce transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), have continued. Mitigation measures to reduce workplace exposures have included work site policies to support flexible work site options, including telework, whereby employees work remotely without commuting to a central place of work.* Opportunities to telework have varied across industries among U.S. jobs where telework options are feasible (1). However, little is known about the impact of telework on risk for SARS-CoV-2 infection. A case-control investigation was conducted to compare telework between eligible symptomatic persons who received positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results (case-patients, 153) and symptomatic persons with negative test results (control-participants, 161). Eligible participants were identified in outpatient health care facilities during July 2020. Among employed participants who reported on their telework status during the 2 weeks preceding illness onset (248), the percentage who were able to telework on a full- or part-time basis was lower among case-patients (35%; 42 of 120) than among control-participants (53%; 68 of 128) (p<0.01). Case-patients were more likely than were control-participants to have reported going exclusively to an office or school setting (adjusted odds ratio [aOR] = 1.8; 95% confidence interval [CI] = 1.2-2.7) in the 2 weeks before illness onset. The association was also observed when further restricting to the 175 participants who reported working in a profession outside the critical infrastructure† (aOR = 2.1; 95% CI = 1.3-3.6). Providing the option to work from home or telework when possible, is an important consideration for reducing the risk for SARS-CoV-2 infection. In industries where telework options are not available, worker safety measures should continue to be scaled up to reduce possible worksite exposures.
View details for DOI 10.15585/mmwr.mm6944a4
View details for PubMedID 33151918
Symptom Duration and Risk Factors for Delayed Return to Usual Health Among Outpatients with COVID-19 in a Multistate Health Care Systems Network - United States, March-June 2020.
MMWR. Morbidity and mortality weekly report
2020; 69 (30): 993–98
Prolonged symptom duration and disability are common in adults hospitalized with severe coronavirus disease 2019 (COVID-19). Characterizing return to baseline health among outpatients with milder COVID-19 illness is important for understanding the full spectrum of COVID-19-associated illness and tailoring public health messaging, interventions, and policy. During April 15-June 25, 2020, telephone interviews were conducted with a random sample of adults aged ≥18 years who had a first positive reverse transcription-polymerase chain reaction (RT-PCR) test for SARS-CoV-2, the virus that causes COVID-19, at an outpatient visit at one of 14 U.S. academic health care systems in 13 states. Interviews were conducted 14-21 days after the test date. Respondents were asked about demographic characteristics, baseline chronic medical conditions, symptoms present at the time of testing, whether those symptoms had resolved by the interview date, and whether they had returned to their usual state of health at the time of interview. Among 292 respondents, 94% (274) reported experiencing one or more symptoms at the time of testing; 35% of these symptomatic respondents reported not having returned to their usual state of health by the date of the interview (median = 16 days from testing date), including 26% among those aged 18-34 years, 32% among those aged 35-49 years, and 47% among those aged ≥50 years. Among respondents reporting cough, fatigue, or shortness of breath at the time of testing, 43%, 35%, and 29%, respectively, continued to experience these symptoms at the time of the interview. These findings indicate that COVID-19 can result in prolonged illness even among persons with milder outpatient illness, including young adults. Effective public health messaging targeting these groups is warranted. Preventative measures, including social distancing, frequent handwashing, and the consistent and correct use of face coverings in public, should be strongly encouraged to slow the spread of SARS-CoV-2.
View details for DOI 10.15585/mmwr.mm6930e1
View details for PubMedID 32730238
Retrospective Analysis of Peri-Intubation Hypoxemia During the Coronavirus Disease 2019 Epidemic Using a Protocol for Modified Airway Management.
2020; 14 (14): e01360
This single-center retrospective study evaluated a protocol for the intubation of patients with confirmed or suspected coronavirus disease 2019 (COVID-19). Twenty-one patients were intubated, 9 of whom were found to have COVID-19. Adherence to the airway management protocol was high. COVID-19 patients had lower peripheral capillary oxygen saturation by pulse oximetry (Spo2) nadirs during intubation (Spo2, 73% [72%-77%] vs 89% [86%-94%], P = .024), and a greater percentage experienced severe hypoxemia defined as Spo2 ≤80% (89% vs 25%, P = .008). The incidence of severe hypoxemia in COVID-19 patients should be considered in the development of guidelines that incorporate high-flow nasal cannula and noninvasive positive pressure ventilation.
View details for DOI 10.1213/XAA.0000000000001360
View details for PubMedID 33449537
Early High-Dose Vitamin D3 for Critically Ill, Vitamin D-Deficient Patients.
The New England journal of medicine
BACKGROUND: Vitamin D deficiency is a common, potentially reversible contributor to morbidity and mortality among critically ill patients. The potential benefits of vitamin D supplementation in acute critical illness require further study.METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D3 supplementation in critically ill, vitamin D-deficient patients who were at high risk for death. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D3 or matched placebo. The primary end point was 90-day all-cause, all-location mortality.RESULTS: A total of 1360 patients were found to be vitamin D-deficient during point-of-care screening and underwent randomization. Of these patients, 1078 had baseline vitamin D deficiency (25-hydroxyvitamin D level, <20 ng per milliliter [50 nmol per liter]) confirmed by subsequent testing and were included in the primary analysis population. The mean day 3 level of 25-hydroxyvitamin D was 46.9±23.2 ng per milliliter (117±58 nmol per liter) in the vitamin D group and 11.4±5.6 ng per milliliter (28±14 nmol per liter) in the placebo group (difference, 35.5 ng per milliliter; 95% confidence interval [CI], 31.5 to 39.6). The 90-day mortality was 23.5% in the vitamin D group (125 of 531 patients) and 20.6% in the placebo group (109 of 528 patients) (difference, 2.9 percentage points; 95% CI, -2.1 to 7.9; P=0.26). There were no clinically important differences between the groups with respect to secondary clinical, physiological, or safety end points. The severity of vitamin D deficiency at baseline did not affect the association between the treatment assignment and mortality.CONCLUSIONS: Early administration of high-dose enteral vitamin D3 did not provide an advantage over placebo with respect to 90-day mortality or other, nonfatal outcomes among critically ill, vitamin D-deficient patients. (Funded by the National Heart, Lung, and Blood Institute; VIOLET ClinicalTrials.gov number, NCT03096314.).
View details for DOI 10.1056/NEJMoa1911124
View details for PubMedID 31826336
End-of-Life Care, Palliative Care Consultation, and Palliative Care Referral in the Emergency Department: A Systematic Review.
Journal of pain and symptom management
CONTEXT: There is growing interest in providing palliative care (PC) in the emergency department (ED), but relatively little is known about the efficacy of ED-based PC interventions. A 2016 systematic review on this topic found no evidence that ED-based PC interventions affect patient outcomes or healthcare utilization, but new research has emerged since the publication of that review.OBJECTIVE: This systematic review provides a concise summary of current literature addressing the impact of ED-based PC interventions on patient- or family-reported outcomes, healthcare utilization, and survival.METHODS: We searched Pubmed, Embase, Web of Science, Scopus and CINAHL from inception until September 1, 2018 and reviewed references. Eligible articles evaluated the effects of PC interventions in the ED on patient- or family-reported outcomes, healthcare utilization, or survival.RESULTS: We screened 3091 abstracts and 98 full text articles with 13 articles selected for final inclusion. Two articles reported the results of a single RCT, while the remaining 11 studies were descriptive or quasi-experimental cohort studies. Over half of the included articles were published after the previous systematic review on this topic. Populations studied included older adults, patients with advanced malignancy, and ED patients screening positive for unmet palliative care needs. Most interventions involved referral to hospice or PC, or PC provided directly in the ED. Compared to usual care, ED-PC interventions improved quality of life, though this improvement was not observed when comparing ED-PC to inpatient-PC. ED-PC interventions expedited PC consultation; most studies reported a concomitant reduction in hospital length-of-stay and increase in hospice utilization, but some data were conflicting. Short-term mortality rates were high across all studies, but ED-PC interventions did not decrease survival time compared to usual care.CONCLUSION: Existing data support that PC in the ED is feasible, may improve quality of life, and does not appear to affect survival.
View details for DOI 10.1016/j.jpainsymman.2019.09.020
View details for PubMedID 31586580
Mechanical Ventilation in Hypoxemic Respiratory Failure.
Emergency medicine clinics of North America
2019; 37 (3): 431–44
Acute hypoxemic respiratory failure (AHRF) is a common challenge in emergency medicine. Patient outcomes depend on interventions performed during preintubation, intubation, and postintubation. The article presents recommendations for evidence-based practice to optimally manage patients with AHRF and the acute respiratory distress syndrome.
View details for DOI 10.1016/j.emc.2019.04.005
View details for PubMedID 31262413
- Metagenomic comparison of tracheal aspirate and mini-bronchial alveolar lavage for assessment of respiratory microbiota AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY 2019; 316 (3): L578–L584
- Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): a randomised phase 2a safety trial LANCET RESPIRATORY MEDICINE 2019; 7 (2): 154–62
- Integrating host response and unbiased microbe detection for lower respiratory tract infection diagnosis in critically ill adults PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2018; 115 (52): E12353–E12362
Critical Care Ultrasound: A Review for Practicing Nephrologists
ADVANCES IN CHRONIC KIDNEY DISEASE
2016; 23 (3): 141-145
The use of point-of-care ultrasound in the intensive care unit, both for diagnostic and procedural purposes, has rapidly proliferated, and evidence supporting its use is growing. Conceptually, critical care ultrasound (CCUS) should be considered an extension of the physical examination and should not be considered a replacement for formal echocardiography or radiology-performed ultrasound. Several CCUS applications are of particular relevance to nephrologists, including focused renal ultrasound in patients at high risk for urinary tract obstruction, real-time ultrasound guidance and verification during the placement of central venous catheters, and ultrasound-augmented assessment of shock and volume status. Each of these applications has the capacity to improve outcomes in patients with acute kidney injury. Although robust evidence regarding long-term outcomes is lacking, existing data demonstrate that CCUS has the potential to improve diagnostic accuracy, expedite appropriate management, and increase safety for critically ill patients across a spectrum of pathologies.
View details for DOI 10.1053/j.ackd.2016.01.015
View details for Web of Science ID 000375348600004
View details for PubMedID 27113689
Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial.
The Lancet. Respiratory medicine
2015; 3 (1): 24-32
No effective pharmacotherapy for acute respiratory distress syndrome (ARDS) exists, and mortality remains high. Preclinical studies support the efficacy of mesenchymal stem (stromal) cells (MSCs) in the treatment of lung injury. We aimed to test the safety of a single dose of allogeneic bone marrow-derived MSCs in patients with moderate-to-severe ARDS.The STem cells for ARDS Treatment (START) trial was a multicentre, open-label, dose-escalation, phase 1 clinical trial. Patients were enrolled in the intensive care units at University of California, San Francisco, CA, USA, Stanford University, Stanford, CA, USA, and Massachusetts General Hospital, Boston, MA, USA, between July 8, 2013, and Jan 13, 2014. Patients were included if they had moderate-to-severe ARDS as defined by the acute onset of the need for positive pressure ventilation by an endotracheal or tracheal tube, a PaO2:FiO2 less than 200 mm Hg with at least 8 cm H2O positive end-expiratory airway pressure (PEEP), and bilateral infiltrates consistent with pulmonary oedema on frontal chest radiograph. The first three patients were treated with low dose MSCs (1 million cells/kg predicted bodyweight [PBW]), the next three patients received intermediate dose MSCs (5 million cells/kg PBW), and the final three patients received high dose MSCs (10 million cells/kg PBW). Primary outcomes included the incidence of prespecified infusion-associated events and serious adverse events. The trial is registered with ClinicalTrials.gov, number NCT01775774.No prespecified infusion-associated events or treatment-related adverse events were reported in any of the nine patients. Serious adverse events were subsequently noted in three patients during the weeks after the infusion: one patient died on study day 9, one patient died on study day 31, and one patient was discovered to have multiple embolic infarcts of the spleen, kidneys, and brain that were age-indeterminate, but thought to have occurred before the MSC infusion based on MRI results. None of these severe adverse events were thought to be MSC-related.A single intravenous infusion of allogeneic, bone marrow-derived human MSCs was well tolerated in nine patients with moderate to severe ARDS. Based on this phase 1 experience, we have proceeded to phase 2 testing of MSCs for moderate to severe ARDS with a primary focus on safety and secondary outcomes including respiratory, systemic, and biological endpoints.The National Heart, Lung, and Blood Institute.
View details for DOI 10.1016/S2213-2600(14)70291-7
View details for PubMedID 25529339
Biomarkers in acute respiratory distress syndrome: from pathobiology to improving patient care
EXPERT REVIEW OF RESPIRATORY MEDICINE
2014; 8 (5): 573-586
Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by alveolar flooding with protein-rich pulmonary edema fluid. Despite an improved understanding of ARDS pathogenesis, our ability to predict the development of ARDS and risk-stratify patients with the disease remains limited. Biomarkers may help identify patients at highest risk of developing ARDS, assess response to therapy, predict outcome, and optimize enrollment in clinical trials. This review begins with a general description of biomarker use in clinical medicine. We then review evidence that supports the value of various ARDS biomarkers organized by the cellular injury processes central to ARDS development: endothelial injury, epithelial injury, disordered inflammation and coagulation, fibrosis, and apoptosis. Finally, we summarize the growing contributions of genomic and proteomic research and suggest ways in which the field may evolve in the coming years.
View details for DOI 10.1586/17476348.2014.924073
View details for Web of Science ID 000342062700007
View details for PubMedID 24875533
Human mesenchymal stem cells reduce the severity of acute lung injury in a sheep model of bacterial pneumonia
2014; 69 (9): 819-825
Human bone marrow-derived mesenchymal stem (stromal) cells (hMSCs) improve survival in mouse models of acute respiratory distress syndrome (ARDS) and reduce pulmonary oedema in a perfused human lung preparation injured with Escherichia coli bacteria. We hypothesised that clinical grade hMSCs would reduce the severity of acute lung injury (ALI) and would be safe in a sheep model of ARDS.Adult sheep (30-40 kg) were surgically prepared. After 5 days of recovery, ALI was induced with cotton smoke insufflation, followed by instillation of live Pseudomonas aeruginosa (2.5×10(11) CFU) into both lungs under isoflurane anaesthesia. Following the injury, sheep were ventilated, resuscitated with lactated Ringer's solution and studied for 24 h. The sheep were randomly allocated to receive one of the following treatments intravenously over 1 h in one of the following groups: (1) control, PlasmaLyte A, n=8; (2) lower dose hMSCs, 5×10(6) hMSCs/kg, n=7; and (3) higher-dose hMSCs, 10×10(6) hMSCs/kg, n=4.By 24 h, the PaO2/FiO2 ratio was significantly improved in both hMSC treatment groups compared with the control group (control group: PaO2/FiO2 of 97±15 mm Hg; lower dose: 288±55 mm Hg (p=0.003); higher dose: 327±2 mm Hg (p=0.003)). The median lung water content was lower in the higher-dose hMSC-treated group compared with the control group (higher dose: 5.0 g wet/g dry [IQR 4.9-5.8] vs control: 6.7 g wet/g dry [IQR 6.4-7.5] (p=0.01)). The hMSCs had no adverse effects.Human MSCs were well tolerated and improved oxygenation and decreased pulmonary oedema in a sheep model of severe ARDS.NCT01775774 for Phase 1. NCT02097641 for Phase 2.
View details for DOI 10.1136/thoraxjnl-2013-204980
View details for Web of Science ID 000340239900009
View details for PubMedID 24891325
View details for PubMedCentralID PMC4284068
- Design and implementation of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of human mesenchymal stem/stromal cells for the treatment of moderate-severe acute respiratory distress syndrome ANNALS OF INTENSIVE CARE 2014; 4
OBLIQUE-AXIS VS. SHORT-AXIS VIEW IN ULTRASOUND-GUIDED CENTRAL VENOUS CATHETERIZATION
JOURNAL OF EMERGENCY MEDICINE
2014; 47 (1): 45-50
Ultrasound (US) guidance during central venous catheterization (CVC) reduces complications and improves success rates compared to landmark-guided techniques. A novel "oblique view" (US transducer held at approximately 45° with respect to the target vessel) has been suggested to be superior to the standard short-axis approach usually used during US-guided CVC.The purpose of this study was to compare the rates of posterior vessel wall puncture (PVWP) between the short-axis and oblique-axis approaches to US-guided CVC.This was a prospective observational trial of emergency medicine residents and attending physicians, using gelatin models to simulate short-axis and oblique-axis US-guided CVC. Participants were blinded to the primary outcome of PVWP. Data collected included year in training/practice, number of central lines placed, time to successful "flash," and self-reported confidence of needle tip position using a Likert scale. After CVC simulation, models were deconstructed and inspected for PVWP.The rate of PVWP was 14.7% using short axis vs. 2.9% using oblique axis, resulting in a difference of 11.8% (95% confidence interval [CI] -4.7-28.3%, p = 0.10) and an odds ratio of 0.2 (95% CI 0.004-1.79). This difference was not statistically significant (p = 0.10). Mean time to flash was 11.9 s using short axis, and 15.4 s using oblique axis (p = 0.14). Confidence in needle tip location was 3.63 using short axis, and 4.58 using oblique axis (p < 0.001).We found decreased PVWP using the oblique axis approach, though the difference was not statistically significant, and participants felt more confident in their needle tip location using the oblique axis view. Further research into the potential benefits of the oblique axis approach is warranted.
View details for DOI 10.1016/j.jemermed.2013.11.080
View details for Web of Science ID 000338476500017
View details for PubMedID 24685453
Impaired Visual Fixation at the Age of 2 Years in Children Born Before the Twenty-Eighth Week of Gestation. Antecedents and Correlates in the Multi Center ELGAN Study
2014; 51 (1): 36-42
Very little is known about the prevalence, antecedents, and correlates of impaired visual fixation in former very preterm newborns.In the multicenter ELGAN study sample of 1057 infants born before the twenty-eighth week of gestation who had a developmental assessment at 2 years corrected age, we identified 73 who were unable to follow an object across the midline. We compared them to the 984 infants who could follow an object across the midline.In this sample of very preterm newborns, those who had impaired visual fixation were much more likely than those without impaired visual fixation to have been born after the shortest of gestations (odds ratio, 3.2; 99% confidence interval, 1.4-7.5) and exposed to maternal aspirin (odds ratio, 5.2; 99% confidence interval, 2.2-12). They were also more likely than their peers to have had prethreshold retinopathy of prematurity (odds ratio, 4.1; 99% confidence interval, 1.8-9.0). At age 2 years, the children with impaired fixation were more likely than others to be unable to walk (even with assistance) (odds ratio, 7.5; 99% confidence interval, 2.2-26) and have a Mental Development Index more than three standard deviations below the mean of a normative sample (odds ratio, 3.6; 99% confidence interval, 1.4-8.2).Risk factors for brain and retinal damages, such as very low gestational age, appear to be risk factors for impaired visual fixation. This inference is further supported by the co-occurrence at age 2 years of impaired visual fixation, inability to walk, and a very low Mental Development Index.
View details for DOI 10.1016/j.pediatrneurol.2014.03.007
View details for Web of Science ID 000338174800008
View details for PubMedID 24938138
View details for PubMedCentralID PMC4062923
Evolving practices in critical care and their influence on acute kidney injury
CURRENT OPINION IN CRITICAL CARE
2013; 19 (6): 523-530
This review highlights the principal advances in critical care over the past year, and discusses the impact of these advances on the diagnosis and management of acute kidney injury (AKI).Recent literature has focused on assessment of volume status and fluid management, particularly in the setting of respiratory and cardiac failure. Other critical care topics are reviewed using a system-based approach.The incidence of AKI appears to be increasing, and despite advances in the provision of critical care and renal replacement therapies, there has been little improvement in its associated morbidity and mortality. Nonetheless, recent advances in critical care will impact the diagnosis and management of AKI, as well as shape the future research agenda. Continued work in the fields of critical care and nephrology will undoubtedly be centered on improved biomarkers for the detection of AKI, specific therapies to mitigate or reverse AKI, and techniques to prevent the development of AKI in the critically ill population.
View details for DOI 10.1097/MCC.0000000000000040
View details for Web of Science ID 000330358100001
View details for PubMedID 24240818
- Cardiac tamponade. The western journal of emergency medicine 2013; 14 (2): 152-?