Active Research

This is unpublished

CURRENT PROJECTS

Assessing efficacy and value of tele-emergency care within the Veterans Health Administration

  • PI: Dr. Kathy Li
  • Co-Investigators: Edwin Wong (UW Department of Health Services), Anita Vashi (VA Palo Alto Health Care System and University of California San Francisco)

Project dates: July 1, 2023 – June 30, 2024
Sponsor: Emergency Medicine Foundation (EMF)
Project Abstract/Summary:
Rationale: Expanding access to emergency medicine expertise beyond the physical emergency department (ED) may improve the efficiency of acute care delivery. Health care spending is of great concern to health systems and payers, with avoidable ED visits being a common target. However, prior research has shown that attempts to divert non-urgent visits to lower acuity sites of care through patient education, financial incentives, extended primary care hours, or nurse advice lines are at best ineffective and at worst lead to dangerous delays in care. A novel care model piloted within the VA, called tele-emergency care (tele-EC), seeks to address Veterans’ acute unscheduled care concerns more efficiently through virtual visits. With tele-EC, callers to the nurse advice line who had an acute concern identified were offered a visit by phone or video with an emergency physician, who evaluated and treated or triaged Veterans as appropriate. Prior analysis of this pilot demonstrated that tele-EC resolved 57% of Veteran concerns virtually while decreasing downstream ED utilization from 35% to 18% in one VA health system. However, as the program expands to more sites, broader evaluation of tele-EC’s impact on efficiency of acute care delivery and identification of an optimal staffing model are needed.
Specific Aims:
Aim 1. To evaluate the effectiveness of tele-EC on patient health-related outcomes and cost
H1: Tele-EC improves the efficiency of acute unscheduled care delivery for a broad range of acute concerns and does so without increasing mortality or hospitalization rates.
Aim 2. To compare patient outcomes and cost for different tele-EC provider types
H2: Sites with tele-EC staffed by emergency physicians have less downstream care utilization and spending than sites staffed by advanced practice providers. These savings will outweigh the marginal cost of emergency physician staffing.

Observation Stays and Readmissions for Older Adults: Implications for Medicare Policies

  • PI: Dr. Amber Sabbatini 
  • Co-Investigators: Joshua M Liao, MD, MSc (Dept of Medicine, Value System Science Lab, UW School of Medicine), Anirban Basu, PhD (Director, CHOICE Institute, UW School of Pharmacy); Brad Wright, PhD (Chair, Dept of Health Services Policy and Management at University of South Carolina); Karen Joynt Maddox, MD, MPH (Co-Director, Center for Advancing Health Services, Policy & Economics Research)

Project Dates: May 2020- - February 2025 (No cost extension)
Sponsor: National Institutes of Health (NIH)
Project Abstract/Summary: Each year, more than 3.4 million Medicare beneficiaries are hospitalized as outpatients under observation. These observation stays have comprised a rapidly increasing proportion of unscheduled hospitalizations among older adults in the US. Controversial Medicare policies, including the Recovery Audit Contractor (RAC) Program and the 2-Midnight Rule, have greatly incentivized hospitals to care for patients via observation instead of an inpatient admission. Additionally, the Hospital Readmissions Reduction Program (HRRP), which penalizes hospitals with higher-than-expected rates of readmissions for certain conditions, may have also had the untoward consequence of incentivizing hospitals to use observation to avoid readmission penalties.

Yet, despite their growing importance in hospital care and the complex policy environment driving their use, few studies have examined how observation stays impact patient’s quality of care and outcomes. Recent evidence shows that 30-day readmissions are increasing among patients with observation stays, despite concomitant declines among inpatients. These disparate trends are significant given that federal quality programs, such as the HRRP, have thus far entirely ignored observation stays in hospital-based care delivery. Similarly, hospitals are not held accountable for other outcomes for patients hospitalized under observation, such as mortality.

As a result, there has been little incentive for hospitals to ensure high-quality and effective care for patients with observation stays relative to inpatients. In this context, this study aims to fill critical gaps in our understanding of the consequences the growth of observation stays on patient outcomes. Using longitudinal Medicare claims and quasi-experimental methods, we will specifically answer the following questions:
1) What is the contemporary national landscape of readmissions, post-discharge ED use, mortality, and acute care costs for patients with observation stays, and how does this compare to inpatients across hospitals?;
2) How have current Medicare payment reforms, including the Recover Audit Contractor (RAC) program, 2-Midnight Rule and HRRP, impacted the use of observation stays, and more importantly, have they had unintended consequences on patient outcomes?;
3) Finally, how should observation stays be accounted for in national quality programs to fully reflect the care needs of older adults requiring hospital care? This study will be the most comprehensive examination to date of outcomes for Medicare beneficiaries with observation stays, and is specifically designed to inform clinical and policy decision-making around observation care for older adults.

Head StART

Achieving HIV viral suppression in refugee settlements in Uganda with Head StART: a cluster randomized trial evaluating the effectiveness of community ART delivery for people newly diagnosed with HI

  • PI: Dr. Kelli O’Laughlin
  • Co-Investigators: Paul Drain, Melissa Mugambi, Deepa Rao, and Monisha Sharma from the UW Department of Global Health; Timothy Muwonge, Andrew Mujugira, and Agnes Kiragga from Infectious Diseases Institute in Uganda.

Project dates: 4/1/2023 – 1/31/2028
Sponsor: National Institutes of Health (NIH)/National Institute of Mental Health (NIMH)
Major goals and Specific aims: The overall objective of this study is to conduct a cluster randomized controlled trial to discern the effectiveness of “Head StART,” community ART delivery for those newly diagnosed with HIV, compared to standard care (facility-based ART delivery) to achieve HIV viral suppression.
Specific Aims: 1) To evaluate the effectiveness of Head StART in achieving HIV viral suppression for people newly diagnosed with HIV in refugee settlements in Uganda; 2) To assess Head StART implementation across refugee settlement locations to understand the impact of contextual factors on achieving optimal HIV clinical outcomes; and 3) To estimate the programmatic cost and budget impact of implementing Head StART in refugee settlements in Uganda. The approach is innovative, in that it assesses novel timing of community ART delivery in a humanitarian crisis affected population at high risk of poor clinical outcomes. The long-term goal is to devise strategies to optimize HIV outcomes in refugee settlements in Uganda.

ICECAP

Influence of Cooling duration on Efficacy in Cardiac Arrest Patients

Project Dates: 7/2020 – Ongoing  
Sponsor: The National Institute of Neurological Disorders and Stroke (NINDS), The National Heart, Lung and Blood Institute (NHLBI) 

Project Abstract/Summary: A multicenter, randomized, adaptive allocation clinical trial to determine if increasing durations of induced hypothermia are associated with an increasing rate of good neurological outcomes and to identify the optimal duration of induced hypothermia for neuroprotection in comatose survivors of cardiac arrest. 

Cardiac arrest is a common and devastating emergency of the heart and the brain. More than 380,000 patients suffer out of hospital cardiac arrest (OHCA) each year in the US. Improvements in cardiac resuscitation (the early links in the “chain of survival” for patients with OHCA) are tempered by our limited ability to resuscitate and protect the brain from global cerebral ischemia. 

Neurological death and disability are common outcomes in survivors of cardiac arrest. Therapeutic cooling of comatose patients resuscitated from shockable rhythms markedly increases the rate of good neurological outcome, but poor outcomes still occur in as many as 50%, and the benefit of cooling in those resuscitated from asystole and pulseless electrical activity has not been shown in a randomized study. 

The overarching goal of this project is to identify clinical strategies that will increase thenumber of patients with good neurological recovery from cardiac arrest. We hypothesize that longer durations of cooling may improve either the proportion of patients that attain a good neurological recovery or may result in better recovery among the proportion already categorized as having good outcome. 
Specific Aims:  A. To determine, in each of two populations of adult comatose survivors of cardiac arrest (those with initial shockable rhythms and those with PEA/asystole), the shortest duration of cooling that provides the maximum treatment effect as determined by a weighted 90 day modified Rankin score B. To determine, in each of two populations of adult comatose survivors of cardiac arrest (those with initial shockable rhythms and those with PEA/asystole), whether increasing durations of cooling are associated with better outcomes or recovery implying efficacy of hypothermia to no cooling. 

TIC 2

Biospecimen collection study evaluating alterations in biomarkers for patients with trauma-induced coagulopathy

Project Dates:  2/2020 – 1/2025 
Sponsor:  National Heart, Lung, and Blood Institute 
Project Abstract/Summary:  Trauma accounts for the greatest number of disability adjusted life-years lost worldwide. In trauma, hemorrhage is the second leading cause of death and the leading cause of preventable death. Trauma induced coagulopathy (TIC) is a common and deadly complication of injury that impairs hemostasis and contributes to hemorrhage. The pathophysiology of TIC is poorly understood but platelet dysfunction has recently been found to play a major role. The normal function of platelets is to adhere at sites of blood vessel injury, activate by releasing stores procoagulant contents, aggregate to form a platelet plug and contract surrounding fibrin to strengthen maturing clot.

The platelets of the TIC patients exhibit severely impaired ability to perform all of these functions but the mechanisms behind these impairments are not well understood. Review of existing literature and some preliminary date reveal several possible causes. First, platelet adhesion and activation could be impaired because of competitive inhibition by protein breakdown products of the binding sites on the platelet cell surface or on VWF(von Willebrand Factor), the primary protein that mediates initial platelet adhesion. Second, despite normal binding site activity, platelets have an impaired response to activation. Specifically, TIC platelets show some evidence of altered release of pro-thrombotic granules in response to activation. 

Specific Aims:  Aim 1: Characterize the defects in the VWF/ADAMTS13/platelet adhesion axis in TIC. Aim 2: Characterize the alterations of platelet surface receptors GPIbα, αIIbβ3, and GPVI in TIC. 

ED INNOVATION

RCT to compare effectiveness of sublingual bup (SL-BUP) versus extended-release bup (XR BUP) in ED patients' engagement in formal addiction treatment.

  • Dr. Lauren Whiteside
    RCT to compare effectiveness of sublingual bup (SL-BUP) versus extended release bup (XR BUP) in ED patients' engagement in formal addiction treatment.

BIOHCA

Biorepository for Out-of-Hospital Cardiac Arrest

Project Dates: February 2022 – Ongoing  
Sponsor: PI Funds 
Project Abstract/Summary: 
Cardiac arrest is the most common cause of death in the United States, with an estimated 320,000 out-of-hospital cardiac arrest (OHCA) victims treated by emergency medical services (EMS) annually. Approximately 60% of patients who achieve return of spontaneous circulation (ROSC) after OHCA die in the hospital.   

The tools that clinicians use to determine neurologic prognosis are imperfect and some have not been validated in the era of modern post-arrest care. Post-cardiac arrest care has evolved rapidly over the past 20 years, and several interventions have been demonstrated to improve outcome. These include targeted temperature management (TTM), early coronary angiography, and meticulous attention to oxygenation and ventilation. A variety of tools are used to assist clinicians when determining prognosis after cardiac arrest, including neurological examination, biomarkers, electroencephalography (EEG), somatosensory evoked potentials (SSEP), and neuroimaging such as magnetic resonance imaging (MRI).   

Biomarkers may identify patients with more severe brain injury after OHCA. Brain injury during cardiac arrest results in inflammation and cell breakdown leading to increased release of biomarkers that reflect the degree of neuronal injury. Several of these biomarkers can be assayed from the plasma or cerebrospinal fluid (CSF). Many studies have examined neuron-specific enolase, derived from neurons, and S-100 protein, derived from glia, but these assays are not readily available at all centers. Creatine kinase (CK) is a dimeric enzyme found primarily in the skeletal muscle and brain that forms adenosine triphosphate from phosphocreatine. The CKBB isoenzyme predominates in brain tissue and leaks from injured brain cells into the cerebrospinal fluid (CSF). In a seminal study that included patients from 1983-1990, elevated CSF CKBB concentrations in the CSF were found to be strong predictors of both never awakening and never regaining independence. In this study of 474 patients who suffered OHCA, zero patients with CSF CKBB concentrations above 205 units/L awoke and only 9 patients with concentrations above 50 units/L awoke; none of these 9 patients regained independence. A subsequent change in the laboratory assay resulted in thresholds for non-awaking being adjusted to 363 units/L and the threshold for predicting independence to 89 units/L. Whether other CSF biomarkers might be useful in determining prognosis is unclear.   

Concentrations of circulating biomarkers predict organ dysfunction and outcome after cardiac arrest. High levels of circulating inflammatory cytokines (e.g. interleukin [IL]-1ra, IL-6, IL-8, IL-10), are common after cardiac arrest. In particular, IL-6 concentrations have consistently been associated with poor outcome after OHCA. In a series of subanalyses of the Targeted Temperature Management randomized trial, elevated concentrations of both pro-inflammatory cytokines and markers (IL-6, procalcitonin and Tumor Necrosis Factor-α (TNF-α)) and biomarkers of endothelial injury (thrombomodulin, sE-selectin, syndecan-1 and VE-cadherin) correlated negatively with mean arterial pressure and vasopressor requirement at 72 hours. These concentrations were not influenced by target temperature. A subsequent study demonstrated that concentrations of both IL-6 and procalcitonin at 24 hours were associated with mortality. Our pilot work demonstrated markedly elevated concentrations of circulating inflammatory mediators after OHCA, which were associated with organ injury and poor outcome. Whether these represent modifiable targets for therapies or simply prognostic indicators, and whether discrete OHCA phenotypes might exist, remains unknown.  
 
Specific Aims: 
1. Build a repository of blood, urine, bronchoalveolar lavage fluid, and cerebrospinal fluid samples linked with clinical data in patients with out-of-hospital and in-hospital cardiac arrest treated at Harborview Medical Center over a 2-year study period.  
2. Test existing and novel biomarkers of neurologic prognosis and organ dysfunction after cardiac arrest.  
3. Phenotype post-cardiac arrest patients according to brain and organ injury patterns and biomarker profiles.  ​​​​​​​

ED LINC

Study Intervention for opioid abuse & linkage to care.

SPARK


A prospective interview-based longitudinal study to learn about health behaviors of young adults seen in Emergency Departments.

BLAZE: Phillips Ultrasound Study

  • Dr. Adeyinka Adedipe
    A prospective observational study to support u/s scanning activities in patients to assess modifications to product design and user preference.

IVY 6
 

Public health surveillance project gathering information about respiratory illnesses and vaccine effectiveness for COVID-19, RSV, and influenza.

PI: Dr. Nick Johnson
Project Dates: Fall 2023 – Fall 2024 
Sponsor: Centers for Disease Control and Prevention (CDC)  
Project Abstract/Summary: Adult Inpatient SARS-CoV-2 Vaccine Effectiveness Surveillance is an observational, multicenter, prospective public health surveillance activity conducted by the Centers for Disease Control and Prevention (CDC) in collaboration with the Influenza and other Viruses in the acutelY ill (IVY) Network.  We will enroll 2 cohorts of hospitalized adults:   

  • Cases with acute infection with SARS-CoV-2, influenza, or respiratory syncytial virus (RSV)   

  • Test negative controls, defined as patients hospitalized with signs and symptoms of an acute respiratory illness (ARI) who test negative for at least one of the target viruses  

We will collect data on prior receipt of COVID-19, influenza, and RSV vaccination (once available) from enrolled patients. By comparing the odds of vaccination among enrolled cases and controls, we will calculate vaccine effectiveness of COVID-19 vaccines for the prevention of COVID-19-associated hospitalizations and of influenza vaccines for the prevention of influenza-associated hospitalizations. Once RSV vaccines are authorized for use, we will evaluate their effectiveness against RSV-associated hospitalizations using similar methods.

We will also estimate vaccine effectiveness for different variants of SARS-CoV-2 and influenza and by baseline patient characteristics, including age group, race/ethnicity, and comorbidity burden and assess the durability of protection by doses.  We will collect an expanded set of biospecimens in a subset of enrolled patients to evaluate biological characteristics of SARS CoV-2 infection and COVID-19 vaccination, including the kinetics and durability of anti-SARS-CoV-2 antibodies intrahost SARS-CoV-2 evolution, and T and B cell responses. Data collected in this surveillance project will be used to serially calculate COVID-19 vaccine effectiveness estimates in the United States and inform CDC public health policies.   
Specific Aims: 

  1. Estimate vaccine effectiveness for COVID-19 vaccines in use in the United States to prevent COVID-19 hospitalization among adults.   

  2. Estimate COVID-19 vaccine effectiveness for the different COVID-19 vaccines in use in the United States for prevention of COVID-19 hospitalizations.   

  3. Estimate COVID-19 vaccine effectiveness against circulating SARS-CoV-2 variants for prevention of COVID-19 hospitalizations.   

  4. Estimate COVID-19 vaccine effectiveness for prevention of COVID-19 hospitalizations within subgroups of the population defined by age, race/ethnicity, and comorbidities, including immunocompromised status.  

  5. Assess the duration of protection for COVID-19 vaccination, including additional or booster vaccine doses.   

  6. Obtain biological specimens to conduct immunologic assessments of COVID-19, influenza, and RSV, the effects of vaccination, mechanisms of vaccine failure, and intrahost virus evolution.  

  7. Estimate vaccine effectiveness for the influenza vaccines in use in the United States to prevent influenza hospitalization among adults.   

  8. Estimate vaccine effectiveness of RSV vaccines, once authorized by FDA for use in the United States, to prevent RSV-associated hospitalization among adults.  

  9. Assess risk factors for severe COVID-19 compared to that caused by other circulating viruses, including influenza and RSV.        

  10. Identify and investigate patients at high risk of intrahost virus evolution using routine genomic surveillance of patients hospitalized with COVID-19.  

  11. Estimate incidence of RSV-associated hospitalizations and consider similar methods for estimating COVID-19-, or influenza-associated hospitalizations.  

LOVED

Study to determine impact of Long COVID-19 on the population.

Project Abstract/Summary: The public health crisis of the past century, the COVID-19 pandemic has led to over a million deaths in the United States (U.S.) as of May 16, 2022.1 Approximately a quarter of the 90 million Americans who have had COVID-19 illness will have symptoms lasting over 3 months after their acute infection.2 This Post-acute sequelae of SARS CoV-2 infection (PASC or Long COVID) illness may affect nearly every organ system, causing a wide variety of health problems and complaints, including headache, fatigue, shortness of breath, chest pain and abdominal pain. In terms of sheer numbers and complexity, Long Covid will challenge the public health system and clinical care in every healthcare site.  

Throughout the pandemic, emergency departments (EDs) have served as the nexus of clinical care, and emergency medicine (EM) physicians have served as the key frontline providers with multiple critical roles in the management of COVID-19 patients. With over 160 million ED visits in the U.S. annually,3 in the coming years EM physicians will undoubtedly care for millions of patients with these symptoms, and they will therefore need evidence-based data to inform ways to distinguish Long Covid from other common illnesses in patients presenting to EDs.  For example, they will need to differentiate shortness of breath (SOB) due to Long Covid from SOB due to acute pulmonary embolism or congestive heart failure. Given their commonality, PASC and other disease entities will also frequently overlap in patients; clinicians will need to understand the pathophysiological and phenotypical interactions between Long Covid and a number of serious, acute illnesses that commonly present to EDs (asthma, congestive heart failure, pulmonary embolism, etc.).   
 
Notably, EDs serve as the main and only healthcare access point for many people facing barriers to primary and preventive care. Individuals who commonly access services in EDs include immigrants, minorities, persons experiencing homelessness, the impoverished, and the under- and uninsured, many of whom have co-morbidities increasing their risk for poor outcomes from COVID-19 and from Long Covid. As the stewards of primary care and public health for large swaths of underserved US populations, EM physicians will need to know how and when to make the diagnosis of Long Covid, as well as principles of outpatient management of Long Covid, including physical therapy and follow-up.   
 
Specific Aims: In this prospective study we seek to determine the prevalence of Long Covid in a broad cohort of patients presenting to the ED. Using Long Covid screening tools and survey instruments, we will prospectively collect data on non-critically ill patients presenting to the ED to determine what percentage of the ED population meets criteria for having Long Covid.  

TOWAR

 Multi-site randomized EFIC trial assessing low titer whole blood resuscitation compared to standard care in prehospital AIRLIFT setting

Project Dates: September 2022 - 2026 
Sponsor: Department of Defense 

Project Abstract/Summary: Initiation of the tenets of damage control resuscitation early, in the prehospital setting, has the potential to reduce downstream complications attributable to hemorrhage by intervening closer to the time of injury, prior to the development of coagulopathy, irreversible shock, and the ensuing inflammatory response.8-11 Thawed plasma transfusion has been shown to safely reduce 30-day mortality when infused early, in the prehospital setting, in patients at risk of hemorrhagic shock and this separation of survival occurs within the first 3 hours. A recent secondary analysis from the PAMPer trial demonstrated that patients who received both plasma and red cells (an independent predictor of mortality in the cohort) in the prehospital setting, had the best adjusted survival. Patients receiving crystalloid resuscitation only had the highest mortality.  

We hypothesize that the initiation of low titer whole blood (LTWB O) resuscitation in the prehospital setting is the most effective resuscitation for those at risk of hemorrhage and significantly reduces the morbidity and mortality attributable to hemorrhagic shock post-injury as compared to standard prehospital resuscitation practice. A large pragmatic clinical trial is needed to definitively establish the efficacy and safety of whole blood resuscitation initiated in the prehospital setting and to characterize its effectiveness as a function of storage time. Only a high-quality clinical trial will provide the evidence to justify the use of this precious blood banking resource early post-injury.  

Study Design/Setting: The current proposed trial will be a 6-year (4-year enrollment), multicenter, open label, prehospital randomized trial utilizing 10 level-1 trauma centers from within the LITES network and will enroll approximately 1020 patients. The University of Pittsburgh will be the Clinical Coordinating Center and the Data Coordinating Center for the study. Study Population: Injured patients at risk of hemorrhagic shock requiring blood transfusion in prehospital phase of care. 
Specific Aims: 

  1. AIM#1: Determine whether prehospital low titer whole blood as compared to standard prehospital resuscitation results in lower 30-day mortality in patients at risk of hemorrhagic shock.  
  2. AIM#2: Determine whether old prehospital whole blood (age > 14 days) as compared to young prehospital whole blood (age ≤ 14 days) is associated with equivalent clinical outcomes, hemostasis, prevention of coagulopathy, and platelet function in patients at risk of hemorrhagic shock.  
  3. AIM#3: Determine whether prehospital low titer whole blood as compared to standard prehospital resuscitation results in lower early mortality endpoints, blood and blood component transfusion requirements, lower incidence of coagulopathy, and improved hemostatic and platelet function in patients at risk of hemorrhagic shock 

Collaborations

TRACK TBI: Study comparing Abbot iSTAT Device to clinical CT in determining traumatic brain injury diagnosis.

Collaboration with UW Department of Neurology

  • Dr. Nancy Temkin & Dr. Christine MacDonald

Trauma Surgery dept - TAP: Randomized intervention trial assessing mortality of trauma patients after receiving Kcentra versus placebo.

Collaboration with UW Department of Surgery, Trauma

  • Dr. Saman Arbabi & Dr. Alex St John
    Randomized, double-blind placebo-controlled trial evaluating KCentra to improve survival in patients with traumatic injury and acute major bleeding.

DEPTH: Randomized intervention trial introducing Doxycycline versus placebo in treating HIV+ individuals with emphysema.

  • Dr. Engi Attia
    This study is a phase II, multicenter, randomized, double-blinded, placebo-controlled clinical trial of 100 mg doxycycline BID for 72 weeks for emphysema in people living with HIV.

OPTIC: Outcomes after Pediatric Trauma and Intensive Care

  • Dr. Elizabeth Killien
    Evaluate how the longitudinal trajectory of post-discharge recovery differs among children surviving critical injury compared to other acute illnesses.

PREVENT: PReventing Emerging infections through Vaccine EffectiveNess Testing—COVID

Collaboration with the Centers for Disease Control

  • Dr. Anne Chipman
    Public health surveillance initiative in collaboration with the Centers for Disease Control and Prevention (CDC) for vaccine effectiveness for healthcare workers.

The Epidemiology of Diagnostic Error in Emergency Care in the United States and the Association with Patient Outcomes and Healthcare Costs

Collaboration with Beth Israel Deaconess Medical Center

  • Dr. Amber Sabbatini, Co-Investigator
    Emergency department (ED) visits are common, with 1 in 5 Americans visiting the ED each year. Diagnostic error is an important problem in healthcare, but there is little evidence from U.S. studies to indicate how often patients who visit the ED are misdiagnosed. This project will measure rates of misdiagnosis in emergency care and how misdiagnosis affects death rates and other patient harms. This project will also evaluate which patients, clinician and hospital factors affect misdiagnosis rates.

 

CareQuest Foundation Simulation Research to Predict Consequences of Adult Dental Medicaid Cuts