Samuel M. Brown

Samuel M. Brown
Intermountain Medical Center · Department of Critical Care

MD MS

About

355
Publications
49,495
Reads
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11,994
Citations
Citations since 2016
242 Research Items
11034 Citations
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Introduction
We run a cutting-edge critical care echocardiography research group with special interest in cardiovascular dysfunction in sepsis and ARDS. I also run the Center for Humanizing Critical Care at Intermountain, focused on using rigorous methods to evaluate and improve the human experience of life-threatening illness and injury.

Publications

Publications (355)
Article
Full-text available
Introduction Survivors of acute respiratory failure (ARF) commonly experience long-lasting physical, cognitive, and/or mental health impairments. Unmet medication needs occurring immediately after hospital discharge may have an important effect on subsequent recovery. Methods and analysis In this multicenter prospective cohort study, we enrolled A...
Article
Rationale: Lung protective ventilation (LPV) improves outcomes for patients with acute respiratory distress syndrome (ARDS), but adherence remains inadequate. Objective: To measure the process and clinical impacts of an implementation science-based intervention to improve LPV adherence for patients with ARDS in part by increased utilization of c...
Article
The SARS-CoV-2 Omicron variant (B.1.1.529 or BA.1) became predominant in the United States by late December 2021 (1). BA.1 has since been replaced by emerging lineages BA.2 (including BA.2.12.1) in March 2022, followed by BA.4 and BA.5, which have accounted for a majority of SARS-CoV-2 infections since late June 2022 (1). Data on the effectiveness...
Article
Rationale: Discussion of patient expectations for recovery is a component of intensive care unit (ICU) follow-up clinics. However, few studies have formally evaluated recovery-related expectations of ICU survivors. Objectives: To estimate the prevalence of unmet expectations for recovery six months after hospital discharge among adult survivors...
Article
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Objective: To compare the effectiveness of a primary covid-19 vaccine series plus booster doses with a primary series alone for the prevention of hospital admission with omicron related covid-19 in the United States. Design: Multicenter observational case-control study with a test negative design. Setting: Hospitals in 18 US states. Participa...
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Platelets and megakaryocytes are critical players in immune responses. Recent reports suggest infection and inflammation alter the megakaryocyte and platelet transcriptome to induce altered platelet reactivity. We examined if non-viral sepsis induces differential platelet gene expression and reactivity. Non-viral sepsis upregulated IFITM3, an inter...
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Background Tixagevimab–cilgavimab is a neutralising monoclonal antibody combination hypothesised to improve outcomes for patients hospitalised with COVID-19. We aimed to compare tixagevimab–cilgavimab versus placebo, in patients receiving remdesivir and other standard care. Methods In a randomised, double-blind, phase 3, placebo-controlled trial,...
Article
Background Test-negative design (TND) studies have produced validated estimates of vaccine effectiveness (VE) for influenza vaccine studies. However, syndrome-negative controls have been proposed for differentiating bias and true estimates in VE evaluations for COVID-19. To understand the use of alternative control groups, we compared characteristi...
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Background Results from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data, including unanalyzed data from trials terminated early, enables more detailed investigation of t...
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Background: Levels of plasma SARS-CoV-2 nucleocapsid (N) antigen may be an important biomarker in patients with COVID-19 and enhance our understanding of the pathogenesis of COVID-19. Objective: To evaluate whether levels of plasma antigen can predict short-term clinical outcomes and identify clinical and viral factors associated with plasma ant...
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Background: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection. Objective: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standa...
Article
In late 2019, SARS-CoV-2 caused the greatest global health crisis in a century, impacting all aspects of society. As the COVID-19 pandemic evolved throughout 2020 and 2021, multiple variants emerged, contributing to multiple surges in cases of COVID-19 worldwide. In 2021, highly effective vaccines became available, although the pandemic continues i...
Preprint
Objectives: To compare the effectiveness of a primary COVID-19 vaccine series plus a booster dose with a primary series alone for the prevention of Omicron variant COVID-19 hospitalization. Design: Multicenter observational case-control study using the test-negative design to evaluate vaccine effectiveness (VE). Setting: Twenty-one hospitals in the...
Article
Unique challenges arise when conducting trials to evaluate therapies already in common clinical use, including difficulty enrolling patients owing to widespread open-label use of trial therapies and the need for large sample sizes to detect small but clinically meaningful treatment effects. Despite numerous successes in trials evaluating novel inte...
Article
Rationale: Uncertainty regarding the natural history of coronavirus disease 2019 (COVID-19) led to difficulty in efficacy endpoint selection for therapeutic trials. Capturing outcomes that occur after hospital discharge may improve assessment of clinical recovery among hospitalized COVID-19 patients. Objectives: Evaluate 90-day clinical course o...
Article
Background COVID-19 mRNA vaccines were authorized in the United States in December 2020. Although vaccine effectiveness (VE) against mild infection declines markedly after several months, limited understanding exists on the long-term durability of protection against COVID-19-associated hospitalization. Methods Case control analysis of adults (≥18...
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Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of lo...
Article
This article has been removed from the AJRCCM website, as it may be revised in the near future.
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Background Coronavirus disease 2019 (COVID-19) has a heterogeneous outcome in individuals from remaining asymptomatic to death. In a majority of cases, mild symptoms are present that do not require hospitalization and can be successfully treated in the outpatient setting, though symptoms may persist for a long duration. We hypothesize that drugs su...
Article
Background The study objective was to evaluate 2 and 3 dose COVID-19 mRNA vaccine effectiveness (VE) in preventing COVID-19 hospitalization among adult solid organ transplant (SOT) recipients. Methods 21-site case-control analysis of 10,425 adults hospitalized March-December 2021. Cases were hospitalized with COVID-19; controls were hospitalized f...
Article
Mortality has historically been the primary outcome of choice for acute and critical care clinical trials. However, undue reliance on mortality can limit the scope of trials that can be performed. Large sample sizes are usually needed for trials powered for a mortality outcome and focusing solely on mortality fails to recognize the importance that...
Article
COVID-19 mRNA vaccines (BNT162b2 [Pfizer-BioNTech] and mRNA-1273 [Moderna]) are effective at preventing COVID-19-associated hospitalization (1-3). However, how well mRNA vaccines protect against the most severe outcomes of these hospitalizations, including invasive mechanical ventilation (IMV) or death is uncertain. Using a case-control design, mRN...
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Objectives To characterize the clinical severity of covid-19 associated with the alpha, delta, and omicron SARS-CoV-2 variants among adults admitted to hospital and to compare the effectiveness of mRNA vaccines to prevent hospital admissions related to each variant. Design Case-control study. Setting 21 hospitals across the United States. Partic...
Article
Rationale: Care of emergency department patients with pneumonia can be challenging. Clinical decision support may decrease unnecessary variation and improve care. Objectives: Report patient outcomes and processes of care following deployment of ePNa: comprehensive, open loop, real-time clinical decision support embedded within the electronic hea...
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Background Accurate methods of identifying patients with COVID-19 who are at high risk of poor outcomes has become especially important with the advent of limited-availability therapies such as monoclonal antibodies. Here we describe development and validation of a simple but accurate scoring tool to classify risk of hospitalization and mortality....
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Background Open-label platform trials and a prospective meta-analysis suggest efficacy of anti–IL-6R therapies in hospitalized patients with COVID-19 receiving corticosteroids. This study evaluated the efficacy and safety of sarilumab, an anti–IL-6R monoclonal antibody, in the treatment of hospitalized patients with COVID-19. Methods In this adapt...
Article
Importance: Sepsis guidelines and research have focused on patients with sepsis who are admitted to the hospital, but the scope and implications of sepsis that is managed in an outpatient setting are largely unknown. Objective: To identify the prevalence, risk factors, practice variation, and outcomes for discharge to outpatient management of se...
Preprint
Objectives: To characterize the clinical severity of COVID-19 caused by Omicron, Delta, and Alpha SARS-CoV-2 variants among hospitalized adults and to compare the effectiveness of mRNA COVID-19 vaccines to prevent hospitalizations caused by each variant. Design: A case-control study of 11,690 hospitalized adults. Setting: Twenty-one hospitals...
Article
Background: In a randomized, placebo-controlled, clinical trial, bamlanivimab, a SARS-CoV-2-neutralizing monoclonal antibody, given in combination with remdesivir, did not improve outcomes among hospitalized patients with COVID-19 based on an early futility assessment. Objective: To evaluate the a priori hypothesis that bamlanivimab has greater...
Article
COVID-19 mRNA vaccines (BNT162b2 [Pfizer-BioNTech] and mRNA-1273 [Moderna]) provide protection against infection with SARS-CoV-2, the virus that causes COVID-19, and are highly effective against COVID-19-associated hospitalization among eligible persons who receive 2 doses (1,2). However, vaccine effectiveness (VE) among persons with immunocompromi...
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Background High-quality leadership improves resuscitation for in-hospital cardiac arrest (IHCA), but experienced resuscitation leaders are unavailable in many settings. Research Question Does real-time telemedical intensivist consultation improve resuscitation quality for IHCA? Study Design and Methods In this multicenter randomized controlled tr...
Preprint
Full-text available
Background Results from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data, including unanalyzed data from trials terminated early, enables more detailed investigation of t...
Article
Background Remdesivir improves clinical outcomes in patients hospitalized with moderate-to-severe coronavirus disease 2019 (Covid-19). Whether the use of remdesivir in symptomatic, nonhospitalized patients with Covid-19 who are at high risk for disease progression prevents hospitalization is uncertain. Methods We conducted a randomized, double-bli...
Article
In a multi-state network, vaccine effectiveness (VE) against COVID-19 hospitalizations was evaluated among immunocompetent adults (≥18-years) during March-August 2021 using a case-control design. Among 1669 hospitalized COVID-19 cases (11% fully vaccinated) and 1950 RT-PCR-negative controls (54% fully vaccinated), VE was higher at 96% (95% CI: 93-9...
Article
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Background Remdesivir (RDV) is a potent nucleotide prodrug inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase that has demonstrated efficacy in the treatment of patients hospitalized with moderate to severe COVID-19. This Phase 3 (GS-US-540–9012) double-blind, placebo-controlled study compared the efficacy and safety of 3 days of RDV to stand...
Article
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Importance: Mechanical power and driving pressure have known associations with survival for patients with acute respiratory distress syndrome. Objectives: To further understand the relative importance of mechanical power and driving pressure as clinical targets for ventilator management. Design: Secondary observational analysis of randomized c...
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Background We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. Methods In this multinational, double-blind, r...
Article
Septic shock is a common deadly disease often associated with cardiovascular dysfunction. Left ventricular longitudinal strain (LV LS) has been proposed as a sensitive marker to measure cardiovascular function; however, it is not available universally in standard clinical echocardiograms. We sought to derive a predictive model for LV LS, using mach...
Article
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-12...
Article
Objective To measure prevalence of discordance between electrical activity recorded by electrocardiography (ECG) and myocardial activity visualized by echocardiography (echo) in patients presenting after cardiac arrest and to compare survival outcomes in cohorts defined by ECG and echo. Methods This is a secondary analysis of a previously publishe...
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Objective To determine whether heart rate variability (HRV; a physiological measure of acute stress) is associated with persistent psychological distress among family members of adult intensive care unit (ICU) patients. Methods This prospective study investigated family members of patients admitted to a study ICU. Participants’ variability in hear...
Article
Background Understanding COVID-19 epidemiology is crucial to clinical care and to clinical trial design and interpretation. Objective To describe characteristics, treatment, and outcomes among patients hospitalized with COVID-19 early in the pandemic. Methods A retrospective cohort study of consecutive adult patients with laboratory-confirmed, sy...
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Background/aims: Safe and effective therapies for COVID-19 are urgently needed. In order to meet this need, the Accelerating COVID-19 Therapeutic Interventions and Vaccines public-private partnership initiated the Therapeutics for Inpatients with COVID-19. Therapeutics for Inpatients with COVID-19 is a multi-arm, multi-stage platform master protoc...
Article
Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome of high morbidity and mortality with global impact. Current epidemiologic estimates are imprecise given differences in patient populations, risk factors, resources, and practice styles around the world. Despite improvement in supportive care which has improved mortality, effecti...
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Systemic capillary leak syndrome (SCLS) is a rare disorder manifesting as shock, hemoconcentration, and hypoalbuminemia, which may be either idiopathic or secondary to an underlying disease process. We report a case of an adult with COVID-19 infection associated with new onset SCLS. Our case joins only two other cases of new SCLS associated with CO...
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Objectives: Access to personal health records in an ICU by persons involved in the patient's care (referred to broadly as "family members" below) has the potential to increase engagement and reduce the negative psychologic sequelae of such hospitalizations. Currently, little is known about patient preferences for information sharing with a designa...
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What is already known about this topic? Two 2-dose mRNA COVID-19 vaccines (from Pfizer-BioNTech and Moderna) and a 1-dose viral vector vaccine (from Janssen [Johnson & Johnson]) are currently used in the United States. What is added by this report? Among U.S. adults without immunocompromising conditions, vaccine effectiveness against COVID-19 hospi...
Preprint
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Objectives: Arterial blood gas measurements are not always immediately available despite their potential relevance to management of mechanically ventilated patients. Retrospective and prospective studies have validated the non-linear imputation of PaO2/FIO2 from SpO2/FIO2, predominantly in USA. In this study, the objective was to validate the non-l...
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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) agai...
Article
Introduction: Understanding patient factors associated with not being vaccinated is essential for successful implementation of influenza vaccination programs. Methods: We enrolled adults hospitalized with severe acute respiratory illness at 10 United States (US) hospitals during the 2019-2020 influenza season. We interviewed patients to collect...
Article
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...
Preprint
BACKGROUND Bamlanivimab, a neutralizing monoclonal antibody given in combination with remdesivir, did not improve outcomes among hospitalized COVID-19 patients based on an early futility assessment. In this final study report, we evaluate an a priori hypothesis that greater benefit of bamlanivimab would be identified in those without detectable end...
Preprint
Full-text available
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 through May 5, 2021, we evaluated vaccine effe...
Article
Full-text available
Background Neutralizing monoclonal antibodies (MAb) are a promising therapy for early COVID-19, but effectiveness has not been confirmed in a real-world setting. Methods In this quasi-experimental pre-/post-implementation study, we estimated the effectiveness of MAb treatment within 7 days of symptom onset in high-risk ambulatory adults with COVID...
Article
Objectives: To understand how patients and family members experience dehumanizing or humanizing treatment when in the ICU. Design: Qualitative study included web-based focus groups and open-ended surveys posted to ICU patient/family social media boards. Focus groups were audio recorded and transcribed. Social media responses were collected and o...
Article
Background Test-negative design studies for evaluating influenza vaccine effectiveness (VE) enroll patients with acute respiratory infection. Enrollment typically occurs before influenza status is determined, resulting in over-enrollment of influenza-negative patients. With availability of rapid and accurate molecular clinical testing, influenza st...
Article
Background: Influenza vaccine effectiveness (VE) against a spectrum of severe disease, including critical illness and death, remains poorly characterized. Methods: We conducted a test-negative study in an intensive care unit (ICU) network at 10 United States hospitals to evaluate VE for preventing influenza-associated severe acute respiratory in...