Background
The COVID-19 pandemic resulted in over 6.8 million deaths worldwide. Although the WHO recently declared an end to the COVID-19 global health emergency, the long-term health impacts from SARS-CoV-2 infection remain unknown. Notably, patients with cardiovascular disease are at increased risk for severe illness and mortality with COVID-19. We sought to understand the inflammatory mechanisms associated with cardiovascular disease that drive severity of COVID-19. To model inflammation in the context of COVID-19, we generated a novel, “humanized” ACE2 (hACE2) mouse that is susceptible to SARS-CoV-2 infection.

Methods
Using CRISPR-Cas9 technology, we inserted the human ACE2 cDNA sequence into the native mouse ACE2 locus, under regulation of the native promoter. Using a combination of RT-qPCR, ELISA, and histology, we validated hACE2 expression in the new strain. Mice underwent intranasal inoculation with SARS-CoV-2 and infection patterns were compared to wild-type mice and the previously characterized K18-hACE2 overexpression model of severe infection. Cultured bone marrow-derived macrophages were subjected to inflammatory stimulation and the dynamic expression of ACE2 expression was assessed for dependence on the NF-kB transcriptional cofactor, Rac1, and the NF-kB-dependent inflammatory cytokine, IL-1β. Chromatin immunoprecipitation (ChIP) was carried out using NF-kB to confirm binding to the ACE2 promoter.

Results
hACE2 mice express human ACE2 mRNA and protein under regulation of the native mouse promoter. Unlike the K18-hACE2, hACE2 mice survived infection with SARS-CoV-2 and maintained stable body weights. Histopathology from the hACE2 mice revealed inflammatory infiltrate and pulmonary consolidation with alveolar hemorrhage, comparable to the K18-hACE2 mice, and immunohistochemistry confirmed presence of viral nucleocapsid in lung consolidations. Infected hACE2 mice demonstrated a unique plasma cytokine profile relative to K18-hACE2 mice, including elevated levels of IL-1β, IL-1α, and VEGF-A, but decreased IL-6 and TNF-α. Bone marrow-derived macrophages revealed increased ACE2 expression in the context of “M1” inflammatory stimulation, and ACE2 expression was dependent on both Rac1 and IL-1β ChIP confirmed NF-kB binding to the ACE2 promoter region. 

Conclusion
We have established a novel model of COVID-19 that survives infection and may facilitate mechanistic studies aimed at understanding the role of inflammation in severity of infection. Macrophages express ACE2 in a dynamic manner and may play a role as a reservoir for ongoing infection during inflammation. Defining Rac1-NF-kB-IL-1β signaling mechanisms driving severity of SARS-CoV-2 infection may identify new targets for inhibiting viral uptake and replication in cells, leading to new therapeutic treatments for patients with COVID-19.


Validation of a Novel Humanized ACE2 Mouse Model of COVID-19

Objective: Since the COVID-19 pandemic began, the number of individuals suffering from mental health disorders has increased substantially without an equal increase in the number of mental health workforce members. This has created difficulty in creating safe discharge plans for hospitalized patients, discouraged patients from seeking necessary help when suffering and can deter patients from completing treatment due to scheduling and financial barriers. The goal of this project is to evaluate availability and cost of outpatient psychiatric and psychological services in the Phoenix, Arizona area. 

Methods: Psychiatry and psychology practices were identified via an online search in the Phoenix, AZ area and contacted by phone or email to enquire about the services they provide. Ten psychiatric and ten psychological practices were contacted. Information was obtained including type of services (psychiatry, psychology, neuropsychiatric testing), type of provider (MD/DO, NP, PA, PhD/PsyD, master’s level counselor, social worker), soonest available appointment and cost of appointment (cash pay vs accepted insurance). Wait times to reach a representative were also recorded. 

Results: For psychiatric services, the average wait time to speak to a representative over the phone was 5 minutes. The average soonest available appointment was 12 days ranging from same day to 5 weeks from date of call. The most common provider available for the soonest available appointment was a physician psychiatrist or NP. Neuropsychiatric testing was offered at 3/10 practices. Insurance was accepted at 8/10 contacted locations, with cash pay costs ranging from $225-450 for intake and $100-300 for each follow up appointment. For psychological services, the average wait time to speak to a representative was 48.5 minutes. The average soonest available appointment was 18 days from date of call ranging from same day to 2 months. The most common provider available for the soonest available appointment was a Psychologist (PsyD/PhD) or master’s level counselor. Neuropsychiatric testing was offered at 4/10 practices. Four practices accepted insurance, all practices accepted cash pay with costs ranging from $75-350 for an intake appointment and $75-265 for each follow up appointment.


Conclusion: In the Phoenix area, access to psychological services including talk therapy and neuropsychiatric testing is more difficult to obtain than psychiatric services. Barriers to these services include longer wait times to speak to representatives for scheduling and information, which can discourage patients from making appointments, longer wait times to the soonest available appointment which can be detrimental to those who are struggling and need help quickly and lack of services covered by insurance. A comprehensive mental health treatment plan often involves both therapy and medication management. This information suggests a focus of increasing both the volume of psychological and psychiatric providers and providers willing to accept insurance to meet the collaborative needs of appropriate mental health care in this location.

Accessibility of Outpatient Mental Health Resources in the GreaterPhoenix, Arizona Area

Background
On March 11, 2020, the WHO declared the COVID-19 outbreak a pandemic. Multiple aspects of healthcare were interrupted, as individuals were instructed to stay home, protect other citizens, and avoid potential exposure. Individuals with HIV heavily rely on healthcare providers for essential medical treatment and critical testing. They are particularly susceptible to the upheaval in healthcare services and access. We undertook this study to evaluate the impact of the COVID-19 pandemic on diverse aspects of HIV patient care. 
Methods
Using the Cascades analysis template provided by the New York State Department of Health populated with our patient data, we compared the effects of the COVID-19 pandemic on established clinic patients on Antiretroviral Therapy (ARV) and whether they received viral load testing (VL) or kept viral load suppression (VS). Established clinic patients had two or more visits to our Infectious Disease clinic for HIV management before COVID-19. We also highlighted differences between viral load testing and suppression status within groups when comparing 2019 and 2021 against 2020. Data were stratified by demographics, including; age 20 to 60 years or older, race (Black, White, Asian), and Ethnicity (Hispanic or Non-Hispanic). The relationship between these outcomes was analyzed via the Chi-square test of independence and logistic regression. A p-value < 0.05 indicated statistical significance. 1,498 patients were seen in our Infectious disease clinic and on antiretroviral therapy during 2019-2021.
Results
A significantly higher percentage of patients did not receive testing in 2020 compared to 2019 & 2021 (OR 0.427, CI [0.237- 0.75], p-value = 0.0035, Chi-square p-value = 0.004). During 2019 & 2021, we observed a higher percentage of detectable patients; however, the year was unlikely to be related to decreased suppression rates (p-value= 0.79). Age is a significant predictor of the outcome for viral testing and suppression (F-value < 0.049, F-value < 0.0001) with an average of 55-56 years. Interestingly, we observed no significant difference in the odds or probability between patient race or ethnicity in obtaining VL testing or achieving suppression.
Conclusion
The observation during our analysis that stood out most prominently was the impact of the COVID-19 pandemic in 2020, likely influenced by nationwide medical facility closures and patient reluctance to leave their homes. Telemedicine appointments were a significant response to COVID-19 and were a tool to combat interruption of care. There is further emphasis on the advantages of home delivery of ARV provided by specialty pharmacies, especially under extreme circumstances. Home medication deliveries, telemedicine visits, and considering age-related factors in HIV-care planning during the earliest part of the pandemic may have prevented deterioration in monitoring these at-risk populations. These findings underscore the imperative of adaptive healthcare delivery methods to navigate the consequences of unforeseen medical emergencies effectively.

Disruptions in the HIV Continuum of Care During COVID-19: Lessons from a Clinic-Based Study

Background

Numerous studies have explored COVID-19 in adults and pediatric patients with chronic illnesses, but limited research has focused on previously healthy children. This study reports results from a COVID-19 screening program implemented at two pediatric clinics in central California, focusing on the clinical presentation of COVID-19 in this population.

Methods

Patients seeking care at the clinics completed a screening questionnaire to identify symptoms consistent with COVID-19. Temperature and oxygen saturation were measured, and nasal swabs were collected for antigen testing. Chief complaints, final diagnoses, and test results were recorded. The severity of COVID-19 illness was categorized using the CDC's severity index.
1) Asymptomatic/ pre-symptomatic - patient reported no symptoms and vital signs were normal.
2) Mild disease - respiratory or GI symptoms were present with or without fever.
3) Moderate disease; evidence of lower respiratory tract involvement was present.
4) Severe disease; oxygen saturation was < 94%.
5) Critical disease; the patient was transferred to the ER for further treatment.

Results

Between 11/2020 and 12/2022, 11,649 COVID-19 antigen screening tests were performed. Patients ranged in age from 0.1 to 17.0 years (mean 8.7, SD 4.5). 47.7% of patients identified as female, 50.5% as male, and 1.8% as other. In total, 1,560 pts. (13.4%) tested positive. Among these, 665 (43%) were asymptomatic/pre-symptomatic, 560 (36%) had mild disease, 318 (20%) had moderate disease, and 17 (1%) had severe disease. No critical cases or transfers to the emergency room were reported. A higher body mass index (BMI) was associated with increased severity of illness. 4,446 patients reported no symptoms at the time of screening. Among these, 85% tested negative, and 15% tested positive. Demographics were similar between these 2 groups. 7,203 patients report symptoms consistent with COVID-19. Among these, 87.6% tested negative and were presumed to have an infection other than COVID-19, while 12.4% tested positive. Median severity of illness did not differ significantly between the 2 groups.

Conclusion

The screening program effectively detected pediatric COVID-19 cases, including asymptomatic patients. In healthy children, COVID-19 was mild, with severity similar to other viral infections. Higher BMI is linked to greater illness severity. These findings enhance understanding of acute COVID-19 in outpatient pediatric populations, emphasizing the need for proper screening to ensure safe delivery of care.

Clinical Manifestations of COVID-19 in Previously Healthy Pediatric Patients Presenting to a Primary Care Office.

Background 
Alarm fatigue is a significant issue for clinicians due to excessive exposure to alarms, leading to desensitization and decreased trust in their accuracy. Further, not all alarms in intensive care settings warrant action or immediate attention. This can result in inappropriate alarm silencing, posing risks to patient care, especially in emergencies. To address this, we propose redesigning alarms with descriptive and directional auditory and visual cues, aiming to reduce cognitive load, improve event detection, reaction time, and user satisfaction.

Methods
We designed auditory alarms to differentiate between moderate and severe changes in blood pressure, aiming to improve accuracy and response time by enhancing alarm contrast for varying levels of urgency. Additionally, we developed a custom heads-up display (HUD) to address visual overload from uninformative alarms contributing to alarm fatigue. VUMC providers participated in two trials of auditory testing (Original vs Modified alarms) and visual testing (simulated ICU monitor vs HUD display). After each trial, participants provided subjective feedback on comfort and user satisfaction using NASA-TLX surveys.

Results
Given that p=0.045 for percent correctness in Original vs. Modified alarms, modified auditory alarms improved accuracy, but not response time (p=0.640). However, given that p=0.147 for percent correctness and p=0.323 for response time in First vs. Second trials, accuracy and reaction times did not improve as trials progressed, perhaps suggesting a steep learning curve in familiarization with varying alarm sounds. Interestingly, NASA-TLX survey scores revealed lower average ratings on the metrics of effort and frustration, suggesting improved user comfort with use of modified alarms. 

Preliminary visual data showed no significant difference in percent correct identifications (p = 0.560) with use of HUD. Interestingly, use of HUD trended towards worse performance which may be attributed to lack of familiarity with novel HUD interface. Several participants expressed that they had difficulty readjusting their visual focus between the HUD screen and laptop screen in real time, likely contributing to higher physical demand ratings. 

Conclusions
Our data shows that auditory modifications to alarms are more effective in clinical and intensive care settings compared to traditional alarms. This could significantly improve clinician accuracy in detecting emergent events, leading to better patient outcomes. Future research should explore integrating both auditory and visual modifications to assess their combined impact on accuracy, response time, and user experience. Although user experience was not improved with modified alarms and HUD display, there is potential to enhance the HUD's comfort, wearability, and compatibility with existing ICU monitors.

Mitigating ICU Alarm Fatigue in Clinicians by Integrating Visual and Auditory Feedback

This project aims to investigate vaccine hesitancy in relation to the COVID-19 pandemic and how social/structural barriers to vaccine access and lack of trustworthiness may impact equitable vaccination rates in African American individuals who reside in the Southeastern US. Current research shows that 46% of participants in a similar study expressed uncertain/low intent to receive the COVID-19 vaccine with factors such as distrust in the efficacy of vaccines influencing intentions most strongly. This project will analyze data from the Southern Community Cohort Study (SCCS), a prospective cohort of approximately 85,000 adults, to examine predisposing, enabling, and need factors from the Andersen Behavioral Model as predictors of vaccine uptake. The results of this study will be presented at scientific conferences, distributed to members of the community, and used to inform dissemination strategies.

Investigating How Social & Structural Barriers to Vaccine Access and Lack of Trustworthiness May Impact Vaccination Rates Among African Americans During the COVID-19 Pandemic

Background: In labor analgesia, epidurals are the gold standard. However, inadequate analgesia in laboring patients with lumbar epidurals is between 1.7-19.8% [1]. Catheter tip location determines which region of the body is anesthetized. During early labor, epidural catheter placement near lumbar nerve roots provides excellent analgesic coverage while catheter placement near sacral nerve roots can lead to inadequate analgesia [2]. While commonly used to predict thoracic epidural placement, the noninvasive epidural stimulation test (EST) has not been tested for predicting lumbar versus sacral epidural placement [3]. In EST, muscle twitching indicates lumbar or sacral nerve root proximity. This study examines EST's ability to predict lumbar versus sacral epidural placement and its labor analgesia quality.

Methods: A single-center, observational study was performed after approval by Stanford University’s Institutional Review Board (reference ID 52856) and submission to the National Clinical Trials Registry (NCT 04109365). After obtaining consent, patients rated their pain on a 0-10 scale (0 = no pain) immediately preceding epidural catheter placement during stage 1 of labor. After epidural catheter placement, EST was performed. The twitching of muscles innervated by the nerve root adjacent to the catheter can be triggered by a typical threshold current of 1.0–9.9 milliamperes. Twitching in the quadriceps indicates lumbar catheter placement. Twitching in the gluteus, hamstring, calf, or foot suggests sacral placement. Analgesic medicine was then delivered. 3 hours later, a 0-10 pain score and loss of cold sensation to ice were recorded. The primary outcome is to identify the efficacy of the EST in determining the epidural catheter's position for labor analgesia in relation to the patient's loss of cold sensation to ice 3 hours later. The secondary outcome was catheter success, defined as self-reported pain score <3 at 3 hours. A two-proportion z-test was used to assess the relationship between activated muscle groups and catheter success.

Results: Primary outcome - Of the 21 patients who completed this study, 19 reported loss of sensation to ice. In all 19, muscle twitching was observed during EST. Secondary outcome - Of the 21 patients who completed the study, 18 experienced twitching in their quadriceps (lumbar plexus group) and 3 experienced twitching in their gluteus, hamstring, calf, or foot (sacral plexus group). In the lumbar plexus group, 16 patients reported a 3-hour pain score <3. In the sacral plexus group, 1 patient reported a 3-hour pain score <3. Using a two-proportion z-test, p=0.0232.

Conclusion: The epidural stimulation test is a valid noninvasive technique to confirm lumbar epidural placement in laboring patients. EST-induced quadricep twitching is associated with better labor analgesia compared to gluteus, hamstring, calf, or foot twitching.

References: [1] Carvalho, B. Failed epidural top-up for cesarean delivery for failure to progress in labor: the case against single-shot spinal anesthesia, Int J Obstet Anesth 2012; 21: 357–9.
[2] Arendt, K., et al. Why epidurals do not always work, Rev Obstet Gynecol 2008; 1(2): 49-55.
[3] Tsui, B., et al. Confirmation of epidural catheter placement using nerve stimulation, Can J Anaesth 1998; 45(7): 640-4.

Early prediction of sub-optimal labor epidural analgesia using electrical stimulation test

Background
Louisiana's Hispanic/Latinx population is a diverse community that has experienced significant growth in recent years. Unfortunately, COVID-19 has disproportionately impacted racial and ethnic minority groups, including Hispanics/Latinx, who often face disparities in healthcare access and outcomes. This study aims to investigate the impact and potential disparities of COVID-19 infection among the Hispanic/Latinx community in Northwest Louisiana.

Methods
A cross-sectional survey was conducted between June 2022 and March 2023. A total of 242 participants were recruited and asked to complete a structured questionnaire. Eligible participants included individuals above 18 years old who identified as Hispanic or Latinx and resided in Northwest Louisiana. Data analysis was conducted using SPSS Version 28 with a statistical significance level set at p < 0.05. Descriptive statistics were utilized to summarize and compare the characteristics of the overall sample, while Pearson’s Chi-squared tests were used to identify risk factors.

Results
The average age of the participants was 42.2 years, 64.7% were female, 56.6% were born in Mexico, 37.7% had attained high school education, 54.1% did not speak English, 61.3% were married, and 51.1% were below the poverty level. Approximately 80% of the study participants had access to COVID-19 testing, with 44.3% receiving testing in a clinical or hospital setting. Among the study participants, 53.6% had been infected with COVID-19. Of those infected, more than half (50.4%) did not receive medical care from a clinic or hospital. Additionally, 63.9% personally knew someone who had suffered severe illness due to COVID-19, and 68% expressed concern about contracting the virus. Factors associated with increased risk of COVID-19 infection included being female, having limited English proficiency, living with 3 or more people, obesity, and asthma.

Conclusion
This cross-sectional survey offers insights into the impact and disparities experienced by the Hispanic/Latinx population in Northwest Louisiana during the COVID-19 pandemic. These findings can aid in implementing prevention measures, resource allocation, and targeted interventions to reduce the risk of COVID-19 and other infectious diseases among minority communities, particularly Hispanics/Latinx.

Disparities and risk factors of COVID-19 infection among Hispanic/Latinx in northwest Louisiana: A Cross-Sectional Study

Background
Pregnant women were one of the most vulnerable populations during the Coronavirus Disease 2019 (COVID-19) pandemic. Understanding how the pandemic influenced prenatal care utilization and birth outcomes of pregnant populations is essential to guiding disaster preparedness in the face of future global threats. We sought to evaluate the COVID-19 pandemic’s influence on the adequacy of prenatal care and birth outcomes.

Methods
Retrospective cohort study compared prenatal care adequacy, diagnostic testing, and gestational age of 481 patients seen at an urban medical center in New York City during the pandemic (October 1, 2020 and October 14, 2020), and in the corresponding pre-pandemic period (October 1, 2019 and October 14, 2019) using student t-test, Mann-Whitney, and chi-squared tests.

Results
Patients seen during the pandemic were more likely to receive Adequate Prenatal Care (OR 2.634 95%CI 1.672-4.184 p < 0.001) than pre-pandemic patients (OR 0.385 95% CI 0.244-0.606 p < 0.001). Adequate Prenatal Care (OR 0.102 95%CI 0.014-0.763 p = 0.005) was negatively associated with early preterm pregnancy (32-36 weeks). There were no statistically significant differences in gestational age between the pre-pandemic and pandemic cohorts (Moderate Preterm 32-36 weeks OR 1.145 95%CI 0.532-2.465 p=0.845, Early Term 37-38 weeks OR 1.049 95%CI 0.658-1.671 p=0.905, Full Term OR 1.044 95% CI 0.689-1.581 p=0.916). 

Conclusion
Though the pandemic imposed unprecedented stresses upon expectant mothers, patients had significantly greater likelihoods of receiving adequate prenatal care during the pandemic, which may be attributed to the expansion of telehealth services and increased health awareness. Despite this increase in prenatal care adequacy, the pandemic had no statistically significant influence on preterm birth rates.

Improving Prenatal Care Adequacy in Urban Settings: Lessons from the COVID 2019 Pandemic

Reducing the Risk of Propagating Retracted Research

There is increasing pressure on social media companies to reduce the spread of misinformation on their platforms. However, they would prefer not to be the arbiters of truth as the truth can be subjective or otherwise hard to determine. Instead, they would prefer that social media users themselves show better discernment when deciding which information to share. Here we show that allowing people to share only those social media posts that they have indicated are true significantly improves sharing discernment, as measured by the difference in the probability of sharing true information versus the probability of sharing false information. Because it doesn’t require social media companies to be the arbiters of truth, this self-censorship intervention can be employed in situations where social media companies suspect that individuals are propagating misinformation but are not sufficiently confident in their suspicions to directly censor the individuals involved. As such, self-censorship can usefully supplement externally imposed (i.e. traditional) censorship in reducing the propagation of false information on social media platforms.


Self-Censorship Appears to be an Effective Way of Reducing the Spread of Misinformation on Social Media

Many people turn to social media for public health information, 
but such platforms often contain conflicting and inaccurate 
medical advice. To assess complex health claims online, 
people may consider the prevailing consensus; however, 
previous work suggests that people may not be very sensitive 
to important cues to consensus “quality”. To explore further, 
across two experiments we tested people’s sensitivity to the 
consensus-quality cues of source diversity and source 
expertise. Via a mock Twitter platform, participants rated their 
belief in a series of health claims both before and after reading 
various kinds of tweets about the claims. Experiment 1 showed 
that experts (both individual medical experts and health 
organisations) were more persuasive than non-experts. 
Additionally, stances that were supported by a diverse set of 
sources were more persuasive. Experiment 2 showed that 
participants continue to favour experts even when 
outnumbered in tweet quantity by non-experts. When experts 
were not present, however, participants favoured high tweet 
quantity. Both experiments suggest that cues to consensus 
quality (namely, expertise and source diversity) and consensus 
quantity (tweet quantity) are salient cues in belief revision. 
These findings are important in understanding how socially 
acquired health information (and misinformation) shifts 
opinion, and the role that experts can play.


Underline digital video library

Validation of a Novel Humanized ACE2 Mouse Model of COVID-19

Accessibility of Outpatient Mental Health Resources in the GreaterPhoenix, Arizona Area

Disruptions in the HIV Continuum of Care During COVID-19: Lessons from a Clinic-Based Study

Clinical Manifestations of COVID-19 in Previously Healthy Pediatric Patients Presenting to a Primary Care Office.

Mitigating ICU Alarm Fatigue in Clinicians by Integrating Visual and Auditory Feedback

Investigating How Social & Structural Barriers to Vaccine Access and Lack of Trustworthiness May Impact Vaccination Rates Among African Americans During the COVID-19 Pandemic

Early prediction of sub-optimal labor epidural analgesia using electrical stimulation test

Disparities and risk factors of COVID-19 infection among Hispanic/Latinx in northwest Louisiana: A Cross-Sectional Study

Improving Prenatal Care Adequacy in Urban Settings: Lessons from the COVID 2019 Pandemic

Reducing the Risk of Propagating Retracted Research

Self-Censorship Appears to be an Effective Way of Reducing the Spread of Misinformation on Social Media

The Influence of Cues to Consensus Quantity and Quality on Belief in Health Claims

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