Improving the timeliness of health expenditure tracking in OECD and low-and middle-income countries

The COVID-19 pandemic has highlighted that access to timely health spending data is crucial for informed policy-making. This Health Working Paper summarises and compares the methodologies applied in around half of OECD countries to estimate public and private health spending for the most recent year (i.e. t-1) as well as the approaches taken by the OECD Secretariat to fill existing data gaps for the remaining OECD countries. For the first time, the paper also explores the feasibility of nowcasting health spending for the current year (i.e. t) and examines data sources that could be potentially useful in such an exercise. While this review should help OECD countries that do not yet have experience in estimating health spending for year t-1 to improve the timeliness in their data reporting, a special focus in this paper lies on testing the applicability of the methods in low- and middle-income countries (LMIC), using the WHO Western Pacific Region (WPRO) as an example. Generally, different data sources exist in many countries that would allow for a more timely estimation for health spending aggregates.

Polytrauma patient with lateral thoracic spondyloptosis: case report and literature review

Background: Spondyloptosis is caused by high force trauma. The vast majority of cases occur in the sagittal plane and at transition points where ridged sections meet more flexible regions. Lateral thoracic spondyloptosis is extremely rare and there is no current consensus on the optimal treatment plan. Case Description: Here we present a case of a previously physically healthy 24-year-old polytrauma patient after he was struck as a pedestrian by a motor vehicle. Of note the patient was found to have lateral spondyloptosis between T9-10 with complete spinal cord transection. The patient also sustained multi-ligamentous left knee injury, pelvic fractures, open comminuted left tibia and fibular fracture, lacerated liver, bilateral renal lacerations, ischemic bowel, and an aortic arch pseudoaneurysm. Conclusion(s): Lateral thoracic spondyloptosis is a devastating injury with an extreme rate of persistent neurologic deficits. There is no unanimously accepted treatment because of the rarity if the injury and the poor outcomes that patients face. Additionally, patients who experience high level trauma often develop severe psychiatric illness, and the importance of identifying risk factors and implementing care early may improve patient outcomes.Copyright © AME Medical Journal.

Impacts of the COVID-19 Pandemic on United States Emergency Medicine Education: A Council of Residency Directors in Emergency Medicine (CORD) Task Force Survey-Based Analysis.

Introduction The COVID-19 pandemic presented unpredicted challenges to Emergency Medicine (EM) education. The rapid onset of the pandemic created clinical, operational, administrative, and home-life challenges for virtually every member of the medical education community, demanding an educational and professional response at all levels including undergraduate medical education (UME), graduate medical education (GME), and faculty. The Council of Residency Directors in Emergency Medicine (CORD) COVID-19 Educational Impact Task Force was established in 2021 to examine these effects and the response of the EM educational community. Methods The Task Force utilized consensus methodology to develop the survey instruments, which were revised using a modified Delphi process. Both open- and closed-answer questions were included in the survey, which was initially distributed electronically to attendees of the 2021 Virtual Academic Assembly. Results were analyzed quantitatively and qualitatively. Results Sixty-three individuals responded to the first part of the survey (which addressed issues related to UME and GME) and 41 individuals responded to the second part of the survey (which addressed faculty and wellness). The pandemic's influence on EM education was viewed in both a positive and negative light. The transition to virtual platforms had various impacts, including innovation and engagement via technology. Remote technology improved participation in didactics and allowed individuals to more easily participate in departmental meetings. However, this also led to a decreased sense of connection with peers and colleagues resulting in a mixed picture for overall engagement and effectiveness. The Task Force has developed a list of recommendations for best practices for EM programs and for EM organizations. Conclusion The survey results articulated the educational benefits and challenges faced by EM educators during the COVID-19 pandemic. Through the challenging times of the pandemic, many institutional and program-based innovations were developed and implemented to address the new educational environment. These approaches will provide invaluable educational tools for future training. This will also prepare the EM academic community to respond to future educational disruptions.

Stable nebulization and muco-trapping properties of regdanvimab/IN-006 support its development as a potent, dose-saving inhaled therapy for COVID-19.

The respiratory tract represents the key target for antiviral delivery in early interventions to prevent severe COVID-19. While neutralizing monoclonal antibodies (mAb) possess considerable efficacy, their current reliance on parenteral dosing necessitates very large doses and places a substantial burden on the healthcare system. In contrast, direct inhaled delivery of mAb therapeutics offers the convenience of self-dosing at home, as well as much more efficient mAb delivery to the respiratory tract. Here, building on our previous discovery of Fc-mucin interactions crosslinking viruses to mucins, we showed that regdanvimab, a potent neutralizing mAb already approved for COVID-19 in several countries, can effectively trap SARS-CoV-2 virus-like particles in fresh human airway mucus. IN-006, a reformulation of regdanvimab, was stably nebulized across a wide range of concentrations, with no loss of activity and no formation of aggregates. Finally, nebulized delivery of IN-006 resulted in 100-fold greater mAb levels in the lungs of rats compared to serum, in marked contrast to intravenously dosed mAbs. These results not only support our current efforts to evaluate the safety and efficacy of IN-006 in clinical trials, but more broadly substantiate nebulized delivery of human antiviral mAbs as a new paradigm in treating SARS-CoV-2 and other respiratory pathologies.

Successful design and execution of two gastric cancer chemoprevention trials in Central America and Puerto Rico

Gastric adenocarcinoma (GAC) is the third leading global cause of cancer mortality and leading infection-associated cancer. The high incidence regions are Latin America, East Asia, and Eastern Europe. In the U.S., GAC represents a major cancer disparity, double the incidence rates in all nonwhite populations, the opposite of Barrett's Esophagus and EAC. Immigrants from high incidence regions maintain the risk profile of their nations of origin. In a paradigm shift, recent guidelines now recommend surveillance endoscopy (eg, 3 years) for patients with high-risk gastric premalignant conditions (GPMCs). Clinical trials of chemoprevention agents for patients with GPMCs are lacking. We conducted two independent, NCI DCP funded, phase II placebo-controlled chemoprevention trials in patients with GPMCs (intestinal metaplasia, atrophic gastritis). The oral agents were curcumin and eflornithine (DFMO). A highly bioavailable preparation of curcumin was used. The RCTs were conducted in Puerto Rico and rural Honduras, with important characteristics: (1) representative of Caribbean and Mesoamerican populations and linked to large U.S. immigrant populations;(2) high prevalence of H. pylori infection and GPMCs;(3) absence of turmeric and curcuminoids in the local diets;(4) proven bidirectional collaboration with academic institutions in the U.S. In the curcumin trial (NCT02782949) H. pylori negative patients were randomized to study drug or placebo for 6 months. In the eflornithine study (NCT02794428), H. pylori positive and negative subjects were randomized to study drug or placebo for 18 months, with endoscopy at baseline, and 6. 18, and 24 months. The primary outcomes were based upon changes in histologic parameters at 6 months. Principal study challenges included: (1) International and bilingual regulatory environment;(2) Strengthening of the research infrastructure, particularly in Central America;(3) Participant recruitment, eg, in the curcumin RCT in Honduras wherein only 10-15% are H. pylori negative;(4) The Covid-19 pandemic;(5) Natural disasters (3 hurricanes). In Conclusion(s): Eflornithine and curcumin RCTs have been successfully completed, despite important challenges in implementation and execution. No losses to follow-up were encountered related to the pandemic or natural disasters. The south-south partnership may provide a model for chemoprevention and translational studies in Latino populations with prevalent cancers such as GAC..

Analysis of Emergency Department Patient-Visit Volumes in an Academic Health System During a COVID-19 Pandemic Statewide 'Safer at Home' Order.

BACKGROUND: We describe patient-visit volumes, patient acuity, and demographics in our 4 academic health system emergency departments (ED) before, during, and after implementation of a COVID-19 pandemic safer-at-home order. METHODS: Data were collected from the electronic health record, including patient-visit volumes, chief complaint, Emergency Severity Index (ESI), and patient demographics. Descriptive statistics were performed. RESULTS: There was a 37% decrease in combined ED patient-visit volume during the safer-at-home order period (42% at the academic medical center). ED patient-visit volumes increased after the safer-at-home order concluded. During the safer-at-home order period, there was an increase in the proportion of ESI-2 visits and admission rates from EDs across the system. CONCLUSIONS: Significant differences in ED patient-visit volumes and patient acuity were associated with a safer-at-home order in our academic health system. These differences are similar to experiences of other hospital systems across the country.

Stable nebulization and muco‐trapping properties of regdanvimab/IN‐006 support its development as a potent, dose‐saving inhaled therapy for COVID‐19

The respiratory tract represents the key target for antiviral delivery in early interventions to prevent severe COVID‐19. While neutralizing monoclonal antibodies (mAb) possess considerable efficacy, their current reliance on parenteral dosing necessitates very large doses and places a substantial burden on the healthcare system. In contrast, direct inhaled delivery of mAb therapeutics offers the convenience of self‐dosing at home, as well as much more efficient mAb delivery to the respiratory tract. Here, building on our previous discovery of Fc‐mucin interactions crosslinking viruses to mucins, we showed that regdanvimab, a potent neutralizing mAb already approved for COVID‐19 in several countries, can effectively trap SARS‐CoV‐2 virus‐like particles in fresh human airway mucus. IN‐006, a reformulation of regdanvimab, was stably nebulized across a wide range of concentrations, with no loss of activity and no formation of aggregates. Finally, nebulized delivery of IN‐006 resulted in 100‐fold greater mAb levels in the lungs of rats compared to serum, in marked contrast to intravenously dosed mAbs. These results not only support our current efforts to evaluate the safety and efficacy of IN‐006 in clinical trials, but more broadly substantiate nebulized delivery of human antiviral mAbs as a new paradigm in treating SARS‐CoV‐2 and other respiratory pathologies.

Pandemic, War, and Global Energy Transitions

The COVID-19 pandemic and Russia's war on Ukraine have impacted the global economy, including the energy sector. The pandemic caused drastic fluctuations in energy demand, oil price shocks, disruptions in energy supply chains, and hampered energy investments, while the war left the world with energy price hikes and energy security challenges. The long-term impacts of these crises on low-carbon energy transitions and mitigation of climate change are still uncertain but are slowly emerging. This paper analyzes the impacts throughout the energy system, including upstream fuel supply, renewable energy investments, demand for energy services, and implications for energy equity, by reviewing recent studies and consulting experts in the field. We find that both crises initially appeared as opportunities for low-carbon energy transitions: the pandemic by showing the extent of lifestyle and behavioral change in a short period and the role of science-based policy advice, and the war by highlighting the need for greater energy diversification and reliance on local, renewable energy sources. However, the early evidence suggests that policymaking worldwide is focused on short-term, seemingly quicker solutions, such as supporting the incumbent energy industry in the post-pandemic era to save the economy and looking for new fossil fuel supply routes for enhancing energy security following the war. As such, the fossil fuel industry may emerge even stronger after these energy crises creating new lock-ins. This implies that the public sentiment against dependency on fossil fuels may end as a lost opportunity to translate into actions toward climate-friendly energy transitions, without ambitious plans for phasing out such fuels altogether. We propose policy recommendations to overcome these challenges toward achieving resilient and sustainable energy systems, mostly driven by energy services.

A randomized, double-blind, Phase 1 study of IN-006, an inhaled antibody treatment for COVID-19 (preprint)

Rationale: Although COVID-19 is predominantly a respiratory tract infection, current antibody treatments are administered by systemic dosing. We hypothesize that inhaled delivery of a muco-trapping monoclonal antibody would provide a more effective and convenient treatment for COVID-19. Objective: We investigated the safety, tolerability, and pharmacokinetics of IN-006, a reformulation of regdanvimab, an approved intravenous treatment for COVID-19, for nebulized delivery by a handheld nebulizer. Methods: A Phase 1 study was conducted in healthy volunteers. Study staff and participants were blinded to treatment assignment, except for pharmacy staff preparing the study drug. The primary outcomes were safety and tolerability. Exploratory outcomes were pharmacokinetic measurements of IN-006 in nasal fluid and serum. Results: Twenty-three participants were enrolled and randomized across two single dose and one multiple dose cohorts. There were no serious adverse events (SAEs). All enrolled participants completed the study without treatment interruption or discontinuation. All treatment-emergent adverse events were transient, non-dose dependent, and were graded mild to moderate in severity. Nebulization was well tolerated and completed in a mean of 6 minutes in the high dose group. Mean nasal fluid concentrations of IN-006 in the multiple dose cohort were 921 microgram/gram of nasal fluid at 30 minutes after dosing and 5.4 microgram/gram at 22 hours. Mean serum levels in the multiple dose cohort peaked at 0.55 microgram/mL at 3 days after the final dose. Conclusions IN-006 was well-tolerated and achieved concentrations in the respiratory tract orders of magnitude above its inhibitory concentration. These data support further clinical development of IN-006.

VACCINATION IS ASSOCIATED WITH DECREASED MORTALITY IN PATIENTS WITH GI BLEEDING AND COVID INFECTION

Introduction: Since the advent of the COVID-19 pandemic, infected patients demonstrate severe coagulation disturbances leading to considerable mortality. COVID-19 vaccination has been shown to not only reduce infection risk but also to improve survival from breakthrough infections. It is not known if COVID vaccination improves outcomes from bleeding. Alabama has one of the lowest vaccination rates in the US. We, therefore, sought to examine the effect of vaccination on patient outcomes with GI bleeding in the setting of a COVID infection in this population. Methods: A retrospective review was conducted of adult patients admitted at a single institution with GI bleeding and COVID infection from May 2020 to October 2021. Inclusion Criteria included patients who had active COVID infection and evidence of GI bleeding (hematemesis, melena, hematochezia or anemia secondary to GI blood loss). Data collected included baseline demographics, vaccination status, mortality, and inpatient treatment including supplemental oxygen requirement, mechanical ventilation, and blood transfusions. The group was dichotomized by vaccination status and clinical outcomes were compared. Results: A total of 113 patients were included in the final analysis. The mean age was 57.3 years (range 19-93), 51.3% were female, and 68.1% identified as White. 44 patients (39.0%) and 63 (61.0%) were vaccinated and unvaccinated, respectively. Vaccinated patients were older than unvaccinated (mean age 63.3 vs. 53.1 years, p=0.003) and more likely to be White (72.7% vs. 50.7%, p=0.03) but had similar gender (%female, 45.5% vs. 54.4%, p=0.44). At presentation, the two groups had similar pulmonary status (vaccinated vs. unvaccinated, need for supplemental oxygen: 11.4% vs. 17.4%, p=0.43;need for mechanical ventilation, 0% vs. 5.8%, p=0.16). Vaccinated patients required significantly fewer blood transfusions (mean, 0.2 units vs. 1.4 units, p=0.03), and this translated to lower mortality (0% vs. 10.1%, p=0.04). In multivariable logistic analysis, the strongest predictor of mortality was lack of COVID-19 vaccination (OR=infinity, p=0.004). Conclusions: In this early analysis, COVID vaccination is associated with decreased mortality related to GI bleeding. This was true even when initial oxygen requirements were accounted for in either of the groups. Further work should be done to elucidate differences in the coagulation cascade in these patient cohorts.(Table Presented)

Anaphylaxis to Pfizer/BioNTech mRNA COVID-19 Vaccine in a Patient With Clinically Confirmed PEG Allergy.

Although allergic responses to the mRNA COVID-19 vaccines are rare, recent reports have suggested that a small number of individuals with allergy to polyethylene glycol (PEG), a component of the mRNA lipid nanoshell, may be at increased risk of anaphylaxis following vaccination. In this report, we describe a case of a patient who received an mRNA COVID-19 vaccine, experienced anaphylaxis, and was subsequently confirmed to have anti-PEG allergy by skin prick testing. The patient had previously noticed urticaria after handling PEG powder for their occupation and had a history of severe allergic response to multiple other allergens. Importantly, as many as 70% of people possess detectable levels of anti-PEG antibodies, indicating that the detection of such antibodies does not imply high risk for an anaphylactic response to vaccination. However, in people with pre-existing anti-PEG antibodies, the administration of PEGylated liposomes may induce higher levels of antibodies, which may cause accelerated clearance of other PEGylated therapeutics a patient may be receiving. It is important to improve awareness of PEG allergy among patients and clinicians.

Recent trends and structure of health spending in OECD countries in the light of economic and public health shocks

Analysis of recent trends in health spending show the two shocks : the economic crisis in 2008 and the recent impact of the COVID 19 in 2020. While OECD economies contracted sharply in 2008 and 2009, the share of health in the economy remained relatively stable. In 2020, with widespread lockdowns and other public health measures severely restricting economic output and consumer spending, many OECD economies went into freefall in 2020. The need to increase health spending, particularly by governments, in response to the pandemic is likely to have led to the fastest growth in OECD health spending in the last 15 years. © 2022 Elsevier Masson SAS

Stable nebulization and muco-trapping properties of Regdanvimab/IN-006 support its development as a potent, dose-saving inhaled therapy for COVID-19 (preprint)

The respiratory tract represents the key target for antiviral delivery in early interventions to prevent severe COVID-19. While neutralizing monoclonal antibodies (mAb) possess considerable efficacy, their current reliance on parenteral dosing necessitates very large doses and places a substantial burden on the healthcare system. In contrast, direct inhaled delivery of mAb therapeutics offers the convenience of self-dosing at home, as well as much more efficient mAb delivery to the respiratory tract. Here, building on our previous discovery of Fc-mucin interactions crosslinking viruses to mucins, we showed that regdanvimab, a potent neutralizing mAb already approved for COVID-19 in several countries around the world, can effectively trap SARS-CoV-2 virus-like-particles in fresh human airway mucus. IN-006, a reformulation of Regdanvimab, was stably nebulized across a wide range of concentrations, with no loss of activity and no formation of aggregates. Finally, nebulized delivery of IN-006 resulted in 100-fold greater mAb levels in the lungs of rats compared to serum, in marked contrast to intravenously dosed mAbs. These results not only support our current efforts to evaluate the safety and efficacy of IN-006 in clinical trials, but more broadly substantiate nebulized delivery of human antiviral mAbs as a new paradigm in treating SARS-CoV-2 and other respiratory pathologies.

WHY AREN'T WE USING TELEMEDICINE MORE? A COMPARISON OF TELEMEDICINE USAGE ACROSS GI AND CANCER CLINICS DURING THE COVID-19 PANDEMIC

Introduction: Telemedicine (TM) usage has exponentially increased during the COVID-19 pandemic with an emphasis on video visits. This trend will likely persist after the pandemic ends. TM can increase access to specialized healthcare services like GI Medicine and cancer care, but successful TM use requires technological readiness for these platforms. We (and others) have shown that TM expansion further exacerbates existing disparities in cancer care with TM underutilized in Black, male, older, and lower income oncology patients during the pandemic. Advanced patient age is most predictive of TM unreadiness. This disparity is exacerbated when considering video visits only. We hypothesize that this inequality will be mitigated when younger patients are compared to an older cohort and sought to test this directly by comparing TM usage between Oncology (older) and GI Medicine (younger) patients during the pandemic. Methods: A retrospective review was conducted of patient visits to a large tertiary referral hospital for patients evaluated in Oncology and GI/Hepatology clinics from March-October 2020. Income was estimated by zip codes using US Census Data. A TM visit was defined as being either video visit or phone call. Logistic multivariable analyses were performed of the entire cohort to predict TM or Video. Results: There were 32,189 Oncology and 13,900 GI patients seen during the study period. In the unadjusted comparison, GI clinic patients were significantly younger, more likely to be male, and more likely to have private insurance. Oncology patients lived farther distances from the hospital and had greater estimated income. GI Clinic patients used both TM and video visits far more often than Oncology patients (Table 1). The two cohorts were propensity matched for age, race, and payer type. The differences in TM (43.6% vs. 3.1%, P<0.001) and video (21.2% vs. 1.6%, P<0.001) visits were even more pronounced for GI patients in adjusted analysis. In multivariable analysis, variables predicting TM usage included younger patient age, gender, race, estimated income, Medicare/Medicaid payer status, and a GI clinic visit predicted video visits usage. The strongest predictor of TM and video visit was a GI/ Hepatology clinic appointment (Table 2). Conclusions: GI patients were evaluated substantially more frequently via TM options than Oncology patients during the COVID-19 pandemic— a finding not driven by traditional predictors of disparities. The perceived mortal nature of cancer care probably pushes both patients and providers toward in-person encounters compared to treatment of chronic GI conditions. With TM effectiveness in expanding healthcare, future work should focus on educating providers and patients in TM use for high anxiety conditions. (Table presented) Comparison of GI Medicine and Oncology Patients During the COVID-19 Pandemic (Table presented) Multivariable Logistic Analysis Predicting Telemedicine and Video Use During the COVID-19 Pandemic

UME-to-GME PandEMonium in COVID-19: Large-Scale Implementation of a Virtual ACGME Milestone-Based Curriculum for Senior Medical Students Matched Into Emergency Medicine.

BACKGROUND: The COVID-19 pandemic displaced newly matched emergency medicine "pre-interns" from in-person educational experiences at the end of medical school. This called for novel remote teaching modalities. OBJECTIVE: This study assesses effectiveness of a multisite Accreditation Council for Graduate Medical Education (ACGME) sub-competency-based curricular implementation on Slack during the first wave of the COVID-19 pandemic in the United States. METHODS: Emergency medicine residency programs were recruited via national organization listservs. Programs designated instructors to manage communications and teaching for the senior medical students who had matched to their programs (pre-interns) in spring/summer 2020. Pre- and post-surveys of trainees and instructors assessed perceived preparedness for residency, perceived effectiveness of common virtual educational modalities, and concern for the pandemic's effects on medical education utilizing a Likert scale of 1 (very unconcerned) to 5 (very concerned). Data were analyzed using descriptive statistics and the t test. RESULTS: Of 276 possible residency programs, 28 enrolled. Of 324 possible pre-interns, 297 (91.7%) completed pre-surveys in April/May and 249 (76.9%) completed post-surveys in June/July. The median weeks since performing a physical examination was 8 (IQR 7-12), since attending in-person didactics was 10 (IQR 8-15) and of rotation displacement was 4 (IQR 2-6). Perceived preparedness increased both overall and for 14 of 21 ACGME Milestone topics taught. Instructors reported higher mean concern (4.32, 95% CI 4.23-4.41) than pre-interns (2.88, 95% CI 2.74-3.02) regarding the pandemic's negative effects on medical education. CONCLUSIONS: Pre-interns reported improvements in residency preparedness after participating in this ACGME sub-competency-based curriculum on Slack.

Flexible Use of Spatial Frames of Reference for Object-Location Memory in Older Adults.

In memory, representations of spatial features are stored in different reference frames; features relative to our position are stored egocentrically and features relative to each other are stored allocentrically. Accessing these representations engages many cognitive and neural resources, and so is susceptible to age-related breakdown. Yet, recent findings on the heterogeneity of cognitive function and spatial ability in healthy older adults suggest that aging may not uniformly impact the flexible use of spatial representations. These factors have yet to be explored in a precisely controlled task that explicitly manipulates spatial frames of reference across learning and retrieval. We used a lab-based virtual reality task to investigate the relationship between object-location memory across frames of reference, cognitive status, and self-reported spatial ability. Memory error was measured using Euclidean distance from studied object locations to participants' responses at testing. Older adults recalled object locations less accurately when they switched between frames of reference from learning to testing, compared with when they remained in the same frame of reference. They also showed an allocentric learning advantage, producing less error when switching from an allocentric to an egocentric frame of reference, compared with the reverse direction of switching. Higher MoCA scores and better self-assessed spatial ability predicted less memory error, especially when learning occurred egocentrically. We suggest that egocentric learning deficits are driven by difficulty in binding multiple viewpoints into a coherent representation. Finally, we highlight the heterogeneity of spatial memory performance in healthy older adults as a potential cognitive marker for neurodegeneration, beyond normal aging.

A Potential Canary in the Coal Mine: A Critical Policy Analysis of the Illinois LSAMP During the COVID-19 Pandemic

The COVID-19 pandemic has continued to impact every industry and test problem-solving capabilities and innovation across the board;education is no exception. As institutions continue to adapt to the impacts of the current public health crisis, colleges and universities are also navigating federal policy prompted by the pandemic. Literature has shown the positive influence of organizations, such as the Louis Stokes Alliances for Minority Participation (LSAMP), and, we argue that they can take a more active intermediary approach, that of an Organizational Buffer, to best support their students during times of uncertainty. Current research highlights the disconnect between STEM education and policy, as well as how the pandemic is disproportionately impacting communities of color. The pervasiveness of whiteness within educational policy and the negative impacts of unequal distribution of resources on students of color in STEM highlight the need to center race in a theoretical framework and policy. The purpose of this study was to understand the policy and communication responses to the pandemic as they pertained to supporting student success in STEM. Using the Theory of Racialized Organizations, which is a qualitative case study approach that leverages diffractive readings, was implemented to understand whether educational policy and communication responses during this time have or perpetuated inequitable systems. Guided by the research question, in what ways do pandemic policies and communications bolster the success of underrepresented minoritized students (URM) majoring in STEM, our study found four versions of policymaking (i.e., Performative, Picking Winners and Losers, Stay in your Lane, and Time Burden) that emerged and did not support URM STEM students equitably and consistently. Based on these findings, we present implications for institutional responses, LSAMP-alliance support, and future research. © Copyright © 2021 Morgan, Callais, Acevedo and Davis.

A phase iia, double-blinded, randomized placebo-controlled trial of mapkapk2 inhibition by ati-450 in treatment of moderate-severe covid-19 pneumonia

RATIONALE: The novel coronavirus disease 2019 (COVID-19) is a rapidly spreading global viral pandemic with a high-risk of mortality in selected populations (i.e. elderly, immunocompromised, cardiopulmonary diseases). A hyperinflammatory state caused by excessive inflammatory cytokine production (i.e. TNFα, IL-1β, IL6, IL-8) has been attributed to the pathobiology of COVID-19-mediated acute respiratory distress syndrome, worsened lung fibrosis and increased mortality. Inflammation and inflammatory disorders signal primarily through the MAPK pathway. Activation of p38α is important for regulating inflammation, and aberrant p38α activation is associated in the pathobiology of diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease and tissue fibrosis. The downstream target of p38α is the protein MAPKAPK2 (MK2) and is responsible for transcriptional production of pro-inflammatory cytokines also elevated in COVID-19 inflammation. Further evidence in other severe viral illnesses (i.e. Dengue, Influenza, CMV) show activation of p38-MK2 signaling axis for mediating inflammation. Potentially, COVID-19 mediated inflammatory cytokine production may signal through p38α-MK2 axis and MK2 pathway blockade may suppress unwanted inflammation. However, it remains unknown whether reducing the inflammatory state can improve COVID-19 outcomes particularly in those with pre-existing conditions. We hypothesized that blockading this pathway would reduce inflammatory cytokine burden and improve respiratory failure-free survival in moderate-severe COVID-19 infected patients. Methods: We designed an investigator-initiated trial (IND#:149790;ClinicalTrials.gov Identifier: NCT04481685) using an oral MK2 inhibitor (ATI-450, Aclaris Pharmaceuticals) in COVID-19. This single-center trial is a Phase IIa, doubleblinded, randomized placebo-controlled proof-of-concept study. COVID-19 positive hospitalized patients with pulmonary signs and symptoms of moderate-severe hypoxic respiratory distress were randomized to ATI-450 or placebo twice-daily for up to 14 days. Results: Study enrollment is completed (n=20 subjects;n=11 male;median age 63 years old). The primary endpoint of this trial is respiratory failure-free survival at 14 days. Secondary endpoints include: changes in WHO-Ordinal scale, additional respiratory and survival outcomes, biochemical assays of circulating cytokines, and safety endpoints. Given the incomplete knowledge of MK2 pathway blockade effects on immune cell function, this study will further explore immune cell characterization in COVID-19 patients treated with ATI-450 via immunophenotyping and 10X Genomics single-cell gene expression analysis. We surmise that myeloid cell activation following COVID-19 infection contributes to localized and systemic tissue injury and will examine the effect of MK2 pathway blockade on eliciting myeloid cell inflammatory activation-suppression. Conclusion: Analyses of the safety, efficacy, and biology of MK2 inhibition, via ATI-450, in treating moderate-severe COVID-19 will be presented.