United States

Background: 
Metabolic syndrome (MetS) is characterized by interrelated metabolic risk factors that increase the risk of cardiovascular disease. With a global prevalence of about 25% in the adult population, prevalence differs across different racial/ethnic populations and is higher in non-Hispanic White (NHW) than non-Hispanic Black (NHB) Americans. Epidemiologic studies have indicated that poor diet quality is associated with fluctuations in blood glucose and dyslipidemia, two essential components of MetS. The study examined the associations between metabolic syndrome (MetS), self-rated dietary quality (SRDQ), and self-rated health (SRH) in non-Hispanic White (NHW) and non-Hispanic Black (NHB) American adults. 


Methods: 
Data (n=3008) from the 2017-2018 US National Health and Nutritional Health Survey were used for this study. Race/ethnic-specific prevalence odds ratio (POR) from multivariable logistic regression analysis was used to evaluate the cross-sectional associations between MetS, SRPDQ, and SRPH. Statistical adjustments were made for age, sex, education, annual household income, alcohol use, smoking, and lack of exercise. 


Results: 
Approximately 39% and 31.2% of NHW study participants with MetS rated their dietary quality and health status as poor compared to 44.7% and 40.8% of NHB with MetS, respectively. SRH was positively correlated with SRDQ in NHW (r=0.281, p &lt;.001) and NHB (r=0.495, p&lt;.001) study participants with MetS. SRPDQ was associated with increased odds of MetS [POR=1.78;95% CI:1.16-2.66] and SRPH [POR=3.73;95% CI: 2.87-4.84] in NHW individuals, and with MetS [POR=1.45;95% CI:1.07-2.83] and SRPH [POR=4.35;95% CI:3.17-5.98] in NHB individuals, controlling for covariates. MetS was associated with increased odds of SRPH in NHW [POR=2.28;95% CI:1.04-3.68] and NHB [POR=2.56;95% CI:1.28-5.12] individuals. SRPDQ was found to mediate the association between MetS and SRPH and increased the association by 25.9% and 46.1% in NHW and NHB individuals, respectively. 


Conclusions: 
This study shows a positive association between SRPDQ and MetS, and that MetS is associated with SRPH in NHW and NHB persons. Longitudinal studies are needed to investigate whether MetS accelerates declines in overall health in NHW and NHB adults and inform clinical and public health interventions to promote optimal dietary quality. Race/ethnic-specific dietary intervention may help prevent and control MetS and its subsequent sequelae, including poor health outcomes.

AMA Research Challenge 2023

Self-rated Dietary Quality, Metabolic Syndrome, and Self-rated Health in non-Hispanic ​Black and non-Hispanic White Americans.

Background: 
Metabolic syndrome (MetS) is characterized by interrelated metabolic risk factors that increase the risk of cardiovascular disease. With a global prevalence of about 25% in the adult population, prevalence differs across different racial/ethnic populations and is higher in non-Hispanic White (NHW) than non-Hispanic Black (NHB) Americans. Epidemiologic studies have indicated that poor diet quality is associated with fluctuations in blood glucose and dyslipidemia, two essential components of MetS. The study examined the associations between metabolic syndrome (MetS), self-rated dietary quality (SRDQ), and self-rated health (SRH) in non-Hispanic White (NHW) and non-Hispanic Black (NHB) American adults. 


Methods: 
Data (n=3008) from the 2017-2018 US National Health and Nutritional Health Survey were used for this study. Race/ethnic-specific prevalence odds ratio (POR) from multivariable logistic regression analysis was used to evaluate the cross-sectional associations between MetS, SRPDQ, and SRPH. Statistical adjustments were made for age, sex, education, annual household income, alcohol use, smoking, and lack of exercise. 


Results: 
Approximately 39% and 31.2% of NHW study participants with MetS rated their dietary quality and health status as poor compared to 44.7% and 40.8% of NHB with MetS, respectively. SRH was positively correlated with SRDQ in NHW (r=0.281, p <.001) and NHB (r=0.495, p<.001) study participants with MetS. SRPDQ was associated with increased odds of MetS [POR=1.78;95% CI:1.16-2.66] and SRPH [POR=3.73;95% CI: 2.87-4.84] in NHW individuals, and with MetS [POR=1.45;95% CI:1.07-2.83] and SRPH [POR=4.35;95% CI:3.17-5.98] in NHB individuals, controlling for covariates. MetS was associated with increased odds of SRPH in NHW [POR=2.28;95% CI:1.04-3.68] and NHB [POR=2.56;95% CI:1.28-5.12] individuals. SRPDQ was found to mediate the association between MetS and SRPH and increased the association by 25.9% and 46.1% in NHW and NHB individuals, respectively. 


Conclusions: 
This study shows a positive association between SRPDQ and MetS, and that MetS is associated with SRPH in NHW and NHB persons. Longitudinal studies are needed to investigate whether MetS accelerates declines in overall health in NHW and NHB adults and inform clinical and public health interventions to promote optimal dietary quality. Race/ethnic-specific dietary intervention may help prevent and control MetS and its subsequent sequelae, including poor health outcomes.

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Purpose: To explore the effects of recalibration on a cardiac surgery risk of mortality (STS-ROM) model in a majority-minority population (25% white). 

Methods: 3,721 patients from 2009-20 were identified in a cardiac surgery registry at a tertiary care center in Hawai'i. Recalibration was performed by training a new model built on only this local data, with in-hospital mortality as a dependent variable, and the following three independent variable strategies: (1) only STS-ROM score (add a flat value), (2) the same independent variables as the original STS-ROM (same model, new coefficients), and (3) entirely new variable selection (local-only model). In keeping with STS methodology, logistic regression models were created with a 70:30 test:train split and optimism-adjusted LASSO variable selection when warranted. Models were evaluated via observed/expected (O/E) ratios and area under the curve (AUC). Clinical impact was evaluated in the test set by comparing classifications of the new models compared to the original STS-ROM risk classification (Low/Medium/High). During this timeframe, STS-ROM was a primary determinant of receiving surgical aortic valve replacement vs transthoracic aortic valve replacement. Thus we also calculated the percentage of aortic valve patients who would have qualified for a different procedure had we used the local model. 

Results: The STS-ROM model underestimated risk overall (O/E: 1.14). Adding a flat value (model 1) performed marginally better (O/E: 1.07) but building a new model (2) using local data and STS-ROM variables performed the best (O/E: 0.99). Model 3, which used only local data, significantly overestimated risk (O/E: 0.82). All models aside from Model 3 had similar AUC (0.82-0.83). If the best model (2) was used instead of the STS-ROM, 3.72% of all patients and 4.1% of non-white patients would have moved up in risk category. Of those already at intermediate risk, 15.6% would have been elevated to high risk. In the aortic valvular population, where STS-ROM was an especially important variable in clinical decision making, 16.7% of surgical replacements may have qualified for less-invasive procedures instead. 

Conclusion: Recalibrating national risk models using local data from our majority-minority population was superior in all models, but entirely new models without national input studies performed worse. Given that these risk models are major factors in surgical decision making, recalibration can have a significant impact on patient care. 


Surgical Risk Models in a Majority-Minority Population: The Clinical Effect of Local Recalibration

Background: The long-term sequelae of undiagnosed and untreated obstructive sleep apnea (OSA) are well-established. Current research supports the existence of racial disparities in prevalence, risk factors, and treatment utilization in OSA. However, most studies focus on adult patients or sample from limited cohorts. The aim of this study is to investigate possible racial disparities in the diagnosis and treatment of OSA in patients aged 0-20 years.
Methods: The TriNetX national database was utilized to identify patients under the age of 22 who were diagnosed with OSA in this retrospective cohort study. The incidence of surgical treatment (tonsillectomy, adenoidectomy, or adenotonsillectomy) and Positive Airway Pressure (PAP) treatment, as well as polysomnography (PSG) rates were examined across multiple races with sub-analyses performed on demographics including age, ethnicity, sex, BMI class, and comorbidities.
Results: We identified 143,111 patients with a diagnosis of OSA using ICD-10 codes across 71 healthcare organizations. 96,181 patients were Caucasian, 41,463 were African American (AA), 4,002 were Asian, 1,127 were American Indians or Alaska Natives (AI/AN), and 338 were Pacific Islanders/Hawaiian Natives (PI/HN). Rates of surgical treatment differed by race (p<0.001), with AA (37.4%), Caucasian (39.5%), AI/AN (37.5%), and PI/HN (34.9%) compared to Asian patients (27.2%). AA (26.3%) and Caucasian (26.4%) children were more likely to obtain a PSG compared to AI/AN (23.8%), Asian (20.2%), and PI/HN (16.9%), p<0.001. In addition, more Caucasian patients (36%) received surgical treatment before 12 years of age compared to AA (34.1%), Asian (24.6%), AI/AN (32.7%), and PI/HN (31.4%) groups (p<0.001) despite AA patients receiving PSG in young children. The adjusted odds of CPAP use were 1.6 times greater for AI/AN vs. Caucasian (95%CI 1.06-2.4) and 1.2 times greater for AA vs. Caucasian (95%CI 1.1-1.3). Significant differences remained after controlling for demographics, BMI, and comorbidities.
Conclusion: There are differential rates of PSG and OSA treatment utilization when analyzed by race in this national sample of pediatric OSA patients. Given the importance of diagnosing and treating OSA early to prevent undesirable outcomes, more studies should be done to confirm these differences and investigate the factors contributing to them.

National Trends in Pediatric Obstructive Sleep Apnea Diagnosis & Treatment Utilization Among Various Racial Groups

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Examining the influence of Demographic Factors and Socioeconomic Variables on Bariatric Surgery outcomes at an Urban Academic Center.

Human Immunodeficiency Virus 1 (HIV-1) is a retrovirus that primarily infects human CD4+ T cells, a key cell-type in the adaptive immune system. The virus establishes a latent reservoir in the early phases of infection that persists in people living with HIV-1 (PLWH) despite effective antiretroviral treatment (ART). Designing strategies to target the HIV-1 reservoir is critical to achieve progress towards a cure. In eukaryotic and prokaryotic cells, and in viruses, antisense transcripts have been shown to exist as long, non-coding RNAs (lncRNA) or coding RNAs (mRNA). Some viruses, like Human T-cell Leukemia Virus Type 1, encode antisense genes to regulate viral expression and replication. HIV-1 antisense transcripts (AST) have been detected in in vitro and ex vivo studies and have been shown to induce viral latency through methylation of histone 3 lysine 27 by recruiting the polycomb repressive complex 2 (PRC2). Our previous studies demonstrated the presence of HIV-1 AST in vivo at levels of 1-3 copies in a median of 5% infected peripheral blood mononuclear cells (PBMC), suggesting a potential role in inducing viral latency in vivo. To determine if HIV-1 AST expression affects levels of plasma viremia, we designed an assay to measure AST expression in PLWH with high viral loads (non-controllers, viral load 5,000-200,000 copies/mL), with low viral loads (viremic controllers, 50-2,000 copies/mL), and with undetectable viral loads (elite controllers, <40 copies/mL). The assay is a limited-dilution, digital PCR approach that targets HIV-1 AST in donor blood cells using donor-specific primers. First, nucleic acid is extracted and subjected to thorough DNase treatment. The remaining antisense RNA is reverse transcribed using a primer targeting the AST region. Detection is achieved with a fluorescent probe and reported as the number of HIV-1 AST molecules per 100 infected cells. We measured AST levels using ACH-2 cells (a model of HIV-1 latency) as a positive control with an average of 3.18 copies of AST per 100 infected cells, as expected. Negative controls included no reverse transcriptase and no template to ensure complete DNA digestion and no mis-priming nor contamination. Our preliminary data includes 4 donor samples in which HIV-1 AST was detected at 1-53 per 100 infected cells. Future studies will determine if AST functions to control HIV-1 replication and induce viral latency in vivo.

Investigation of HIV-1 Antisense Expression In Vivo

Mucosal immunity to SARS-CoV-2 is crucial in attenuating viral replication. While intramuscular mRNA vaccination has been shown to produce durable SARS-CoV-2 specific antibody responses in the systemic circulation, there are few studies pertaining to local responses in the nasal mucosa. The extent to which vaccination may recall nasal antibody responses primed by prior infection or if nasal antibody responses to infection are primed by prior vaccination remains unelucidated. In the present study, we compared SARS-CoV-2 specific nasal antibody responses among unvaccinated infected, vaccinated infected, infection-experienced vaccinated, and infection-naïve vaccinated participants.

Between June 2020 to February 2023, nasopharyngeal swab (NPS) samples were collected from participants as part of an ongoing longitudinal surveillance study. Samples collected within 14-89 days after either confirmation of an acute SARS-CoV-2 infection via RT-PCR or vaccination with a third mRNA dose were selected for the present study. Secretory-IgA (SIgA) and IgG responses to the Spike antigen of ancestral (B.1 lineage) SARS-CoV-2 were measured via enzyme-linked immunosorbent assay. SIgA was normalized to total-IgA concentration. Nonparametric continuous variables were analyzed using the Kruskal-Wallis test followed by Dunn’s multiple comparisons test. Paired groups were compared using Wilcoxon signed-ranked test. This study was approved by the Children’s Hospital Los Angeles Institutional Review Board.

Of 429 NPS samples, 176 (41.0%) were from male participants, and the mean age at collection was 27.7 years (range, 0.1-81.3 years). Median SIgA concentrations (x10 3 AU/mL) were 39.2 (unvaccinated infected), 230.2 (vaccinated infected), 22.1 (infection-experienced vaccinated), and 5.3 (infection-naïve vaccinated). Median IgG concentrations (x10 3 AU/mL) were 2.2 (unvaccinated infected), 16.0 (vaccinated infected), 5.4 (infection-experienced vaccinated), and 4.4 (infection-naïve vaccinated).

SIgA and IgG were significantly higher in vaccinated infected participants compared to unvaccinated infected (p<0.001), infection-experienced vaccinated (p<0.001), and infection-naïve vaccinated (p<0.001) participants.
SIgA was significantly lower in infection-experienced vaccinated participants compared to unvaccinated infected (p=0.045) participants whereas the opposite trend was observed for IgG (p<0.001).

Acute COVID-19 infection robustly induces SARS-CoV-2 specific nasal SIgA and IgG
responses in vaccinated participants to a greater extent than infection alone. Infection-experienced vaccinated individuals elicit a weaker SIgA response compared to infection alone, indicating that vaccination cannot completely recall nasal SIgA responses. Acquiring a better understanding of SARS-CoV-2 specific nasal antibody responses is an important step towards developing vaccines that can elicit strong mucosal immunity.

Nasal SARS-CoV-2 specific secretory-IgA and IgG are robustly induced in vaccinated individuals after infection

Background: The WHO reported 132 million cases and 2.8 million deaths from COVID-19 through 2021, with severe cases resulting in multi-organ failure. The Sequential Organ Failure Assessment (SOFA) score measures multi-system organ failure changes overtime. The ability to predict outcomes of critically ill COVID-19 patients would advance allocating resources, better managing this disease. To combat mortality, many potential therapies were studied to manage COVID-19’s lethal effects, one being Azithromycin. While it is safe as treatment for bacterial infections, its effectiveness as treatment for COVID-19 is controversial. Given risks associated with blanket antibiotic use, we sought to evaluate azithromycin’s effectiveness as treatment for COVID-19.

Methods: This is a retrospective, non-controlled, two-center study of consecutive adult (age >18) COVID-19 positive cases admitted at two hospitals in Ventura, California from March 2020 to March 2021. We aim to determine the effect of Azithromycin therapy on SOFA scores, hospital stay duration, and mortality among ICU COVID-19 patients.

Results: 857 patients were admitted between two hospitals for the study period. 46% (N=392) received treatment for COVID-19. 37.8% received Azithromycin as a therapy exclusively or as combination. In the treatment group (N=148), mean age was 57.58±18.70, mean BMI was 31.75±9.1, mean length of stay was 8.26±7.37 days, mean minimum O2 saturation was 79.44±15.26, and mean peak SOFA score was 3.21±3.80. There were 99 (67%) males and 49 (33%) females (P<0.01). 96 (65%) patients self-identified as Hispanic/Latino (P<.01); 62 (42%) were admitted to the ICU. The mortality rate for the treatment group was higher compared to control, but not significantly (17.6 vs. 10.7, P=0.06). Peak SOFA scores were significantly different in the treatment group between those who survived and those who did not (3.9 vs, 10.7, P<0.01).

Conclusion: Azithromycin’s effectiveness at reducing inflammatory markers made it a prominent treatment contender for tempering the COVID-19 cytokine storm, along with data suggesting azithromycin effects viral integration and replication in vitro(10). We found no significant benefit from use of azithromycin in COVID-19 patients. However, despite the treatment group being smaller than control, mortalities were equal. Though not statistically significant, higher mortality was seen after administration of azithromycin to COVID patients. Like other studies, we found no association between the use of Azithromycin in COVID-19 patients and mortality, length of hospital stay, or need for mechanical ventilation(8, 9). Given risk from antibiotic use in large populations without significant benefit, we recommend against the use of azithromycin in COVID-19 patients.

Azithromycin Therapy and its Correlation to the Sequential Organ Failure Assessment, Intensive Care Admission, and Mortality among Hospitalized COVID Positive Patients

Background: Antimicrobial stewardship programs (ASP) are a key component of efforts to combat antimicrobial resistance. These programs are designed to reduce to non-indicated use of antimicrobials, reduce adverse drug reactions, and provide guidance for the indicated uses of antimicrobials. We audited adherence to vancomycin use guidelines to determine if prescribers are compliant with vancomycin use guidelines and calculated the rate of non-indicated vancomycin use through chart review. 
Methods: We reviewed vancomycin prescriptions for four months in 2022 and determined if vancomycin use was indicated according to hospital guidelines. Chart review consisted of evaluating the clinician’s stated reason for starting vancomycin, if that indication was adherent to guidelines, and the duration of antibiotic use. We compared the total number of vancomycin prescriptions during this period to nonindicated prescriptions during this time period. 
Results: The rate of non-indicated vancomycin use was 4.8%. The most common non-indicated use of vancomycin was when there was no identifiable or presumed bacterial infection (36.4% of non-indicated use). The second most common reason was the organism was susceptible to a first line antibiotic (32.7%). The third most common reason was the prescription of vancomycin for community acquired pneumonia (CAP) with low a MRSA risk (29.1%).
Conclusion: 95.2% of vancomycin orders were adherent to hospital policy. Adherence to ASP guidelines reduces vancomycin misuse and promotes antibiotic de-escalation. This reduces the amount of unnecessary vancomycin use within the hospital and protects patients from unnecessary antibiotic exposure. 


Are Vancomycin Use Guidelines Followed in a Community Hospital? 
Examining Vancomycin Prescriptions Through Retrospective Chart Review

Background
Most of the available COVID-19 outcome data in Solid Organ Transplant (SOT) recipients does not suggest a higher mortality rate in the SOT population. Though theoretically immunosuppressive medications might be associated with worse outcome, its immunomodulatory effect might be beneficial.

Methods
We retrospectively analyzed the effect of dose-reduction of mycophenolate, tacrolimus, and prednisone on the severity of COVID-19 in SOT recipients diagnosed with COVID-19 at the Center for Transplantation of the University of Kansas Medical Center between January 1, 2020 and December 31, 2022. Severe COVID-19 was defined as development of hypoxia while the patient is on room air during a 21-day period following COVID-19 diagnosis. To evaluate the effect of dose changes after the diagnosis of COVID-19 on the odds of severe COVID-19, we subset our data based on whether patients were taking mycophenolate (n = 449), tacrolimus (n = 537) or prednisone (n = 386) at the time of diagnosis. Within each subgroup, we fit a logistic regression model with severe COVID-19 as the response variable and adjusted for the relevant immunosuppressant and a set of covariates.

Results
In our SOT population, 570 patients were diagnosed with COVID-19 (458 kidney, 73 liver, 54 heart, 43 pancreas, and 8 lung recipients). The median patient age was 54 years, 59% were male, and 70% were white. After adjusting for other covariates, a mycophenolate dose-reduction of < 50% was associated with an odds ratio of 1.89 (95% CI: 0.96-3.70; p=0.06) for developing severe COVID-19. Similarly, decreasing the dose of mycophenolate by  50% was associated with an odds ratio of 2.44 (95% CI: 1.02-5.85, p=0.05) for developing severe disease. Tacrolimus dose reduction did not increase the risk of severe COVID-19. An increase or a decrease of prednisone dose was not associated with severe COVID-19. 

Conclusion
The reduction of mycophenolate dose when a SOT patient is diagnosed with COVID-19 should be discouraged, especially if the patient has mild disease.

Reducing the dose of Mycophenolate in Solid Organ Transplant Recipients Diagnosed with SARS-CoV-2 Infection Increases the Risk of Severe COVID-19

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 
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.

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Surgical Risk Models in a Majority-Minority Population: The Clinical Effect of Local Recalibration