United States

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 &lt; 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. 


AMA Research Challenge 2023

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

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.

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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.

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

Background:
Unintended perioperative hypothermia, defined as having a core-body temperature less than 36 degrees Celsius, occurs in 78.6 % of patients undergoing general anesthesia. Additionally, it is also seen post-operatively in the SICU as well. Concurrently, peri and postoperative hypothermia is also associated with higher rates of infection, increased recovery time, cardiovascular diseases, perioperative hemorrhage, and impairment of drug metabolism. Therefore, it is crucial to limit the incidence of peri and postoperative hypothermia because it is both adjustable and advantageous for the patient. Doing so limits postoperative complications and future surgical interventions. The research goal was to determine the efficacy of using either a water-circulating device or a forced air warming system maintaining both peri/postoperative normothermia during thoracic and abdominal surgeries.

Methods:
A systematic review of randomized controlled trials and non-randomized studies addressing the efficacy of surgical warming systems was conducted. The impact of a water circulating device and a forced air warming system on maintaining peri and postoperative normothermia during abdominal and thoracic surgical procedures were analyzed.

Results:
The initial search of databases returned a total of 28 publications. Five total randomized controlled studies and non-randomized studies were included and analyzed in this review. There was a statistically significant difference in mean core body temperature in patient’s using the water-circulating device when compared to the forced air warming system during thoracic and abdominal procedures perioperatively in both the randomized controlled studies and non-randomized studies, mean difference of 0.45, p=0.0002, 95% CI [0.21,0.69] and mean difference of 0.47, p=0.001, 95% CI [0.18,0.75], respectively. There was not a statistically significant difference in mean core body temperature in patient’s using the water-circulating device when compared to the forced air warming system during thoracic and abdominal procedures postoperatively in the randomized controlled studies, mean difference of 0.41, p=0.34, 95% CI [-1.08,1.33]. There was a slight difference in the maintenance of normothermia postoperatively in the nonrandomized studies, mean difference of 0.89, p=0.02, 95% CI [0.12,1.65].

Conclusion
The investigated water warming system results in better maintenance of intraoperative normothermia than routine air forced warming applied to the upper and lower body.


Water Circulating Device versus Forced Air Warming System in Prevention of Hypothermia during Thoracic and Abdominal Surgeries: a Meta Analysis

Background: In the last 20 years, African Americans and Hispanics/Latinos have been less likely to receive treatment of any analgesia, including opioids as compared to Whites/Caucasians. Surgery and anesthesia are critical healthcare services and are the mainstay treatment for many pathologies, however, postoperative pain is often a significant concern for surgical patients. Poorly controlled acute postoperative pain is associated with diminished function and mobility, delayed recovery, prolonged opioid use, and higher healthcare costs. Although evidence of disparities in the treatment of pain exists, studies on this topic are limited.
Methods: A systematic review and meta- analysis of cohort studies and cross-sectional analysis of studies published in PubMed, Embase, and Scopus in the last 10 years examining disparities in perioperative pain treatment specifically the use of regional anesthesia and opioid use measured in milligrams of morphine equivalents (MME). Articles with sample populations from the United States examining were included, data from Obstetric, Pediatric (<18 years old), and simulation cases were excluded.
Results: The initial search yielded 640 articles, after abstract and full-text screening 5 studies met the inclusion criteria. The types of surgery included in the review were mastectomy, thoracic surgery, and abdominal surgery. The odds of receiving regional anesthesia of minority populations as compared to whites found to be as follows with: Blacks 0.78 [95% CI: 0.73- 0.82]P<0.00001 and I2 =97%, Asian 0.58[95% CI: 0.54-0.63] ]P<0.00001 and I2 =98%, other
Ó 2023 American Medical Association. All rights reserved.
0.85[95% CI: 0.75-0.96] P=0.83 and I2=0%, Native Hawaiian 0.85[95% CI: 0.63-1.14]P=0.28, Native American 0.93[95% CI: 0.71-1.23] P<0.62. Studies had a significant heterogeneity in reporting opioid consumption; thus, meta-analysis was not feasible. However, some studies did show differences in opioid prescription among minority groups showing the need for more standardized research in the area.
Conclusion: Analysis of existing data demonstrates that overall self-identified minority individuals had lower odds of receiving regional anesthesia for pain control as compared to white/Caucasian patients undergoing the same procedures; thus, highlighting a disparity in acute perioperative pain control The sparse number of available studies in the literature focusing on disparities in acute perioperative pain control poses a challenge to accurate evaluation. The high heterogeneity amongst the studies also limits the strength of evidence. In light of the paltry reporting of disparities in peri-operative pain control, more studies are needed to identify the true nature and size of the underlying issue so the root cause may be elicited and corrected in order to improve health equity.

Disparities in Perioperative Pain Control: A Systematic Review and Meta- Analysis

Background:
Sex differences in cardiac arrhythmias are well-established and partly attributed to sex hormones. We aimed to explore the prevalence of arrhythmias in transgender and nonbinary (TGNB) adults.
Methods:
This cross-sectional study utilized patient electronic medical records from a single communityhealthcare center specializing in TGNB care. Adults aged >18 years with >2 medical visitsbetween January 1, 2010, and December 31, 2021, were categorized into self-reported gender groups as TGNB (transgender man[TGM], transgender woman[TGW], nonbinary–assigned male at birth, nonbinary–assigned female at birth) and cisgender (cisgender man[CisM] or cisgender woman[CisW]). We categorized arrhythmias as atrial, ventricular, or other. Descriptive statistics
characterized the prevalence of arrhythmias by gender group. Age- and race-adjusted Firth-type logistic regression models compared TGNB patients to CisM and CisW. The prevalence of arrhythmias was also descriptively explored in nonbinary people and in TGNB people with a gender-affirming hormone therapy (GAHT) prescription .
Results:
Among 49,862 adults, 7121 (14%) identified as TGNB persons. Participants were young (median age 28 years-old) and prevalence of arrhythmias was low (0.7-1.4% in NB persons, 1.4-1.5% in TG persons). Adjusting for age and race, TGM and TGW had a similar risk of arrhythmias compared to CisM (TGW: OR=0.89 (0.63-1.24), p=0.52; TGM: OR=1.17 (0.82-1.62), p=0.37), but statistically significantly higher odds of arrhythmias compared to CisW (TGW: OR=1.65 (1.13-2.34), p=0.01; TGM: OR=2.15 (1.48-3.04), p<0.01). Prevalence of arrhythmias appeared similar among TGNB adults who used GAHT and those who did not (1.5% vs 1.9% in TGM, 1.2% vs 2.1% in TGW).
Conclusion:
Further research examining arrhythmias in TGNB patients and across gender minority subgroupsis warranted, including longitudinal studies evaluating the potential impact of GAHT.

Prevalence of Cardiac Arrhythmias in Transgender and Nonbinary Community Adult Health Center Patients

Background
Major depressive disorder is a relatively common comorbidity among patients living with human immunodeficiency virus (PLWH). However, it is not clear if its impact on the outcomes of cardiovascular diseases is modified by other coexisting conditions. We aimed to stratify the differences in outcomes, based on certain high-risk behaviors, between PLWH with and without depression, who have been hospitalized due to acute myocardial infarction (AMI).
Methods
Using the International Classification of Diseases, tenth Revision, Clinical Modification (ICD-10-CM), we queried the national inpatient sample (NIS) database to identify PLWH who have been hospitalized with AMI from 2010 to 2019. Mortality rate, frequency of home disposition (HD), length of hospital stay (LOS), and total hospital charge (THC) were compared between PLWH with AMI and depression and those without depression. A similar comparison was stratified based on co-existence of sleep disorder (SD), drug abuse (DA), and alcohol dependence (AD).
Results
Data of 1,816,567 admission cases were identified for PLWH, from which 1.8% of patients had a discharge diagnosis of AMI. Of the 29,203 admissions for PLWH with AMI, 10.8% had a diagnosis of depression, 2.7% with a diagnosis of a SD, 44.7% with DA, and 3.7% with AD. Overall, 9.4% of PLWH with AMI died during the hospital stay. Co-existence of depression was associated with a significantly lower mortality rate compared to those without depression (4.9% vs. 9.9%, p<0.0001). Similarly, HD was more frequent among those with depression than those without depression (61.7% vs. 56.9%, p=0.02). The presence of depression was associated with a significantly shorter LOS (6.2 days vs. 7.8 days, p=0.003) and lower THC ($94,385.2 vs. $114,808.7, p=0.01). Among PLWH with AMI and depression, the co-existence of SD was associated with a lower prevalence of HD while co-existence of DA was associated with a higher frequency of HD. Co-existence of DA was also associated with a shorter LOS and lower THC among the cohorts of PLWH and AMI with and without depression. Such a pattern was not significantly different between the same cohort based on AD.
Conclusion
PLWH who are hospitalized due to AMI have a lower mortality rate in the presence of depression, sleep disorder, drug abuse, and alcohol dependence. However, co-existence of these comorbidities is associated with variable impact on the chance of home disposition, length of stay, and hospital charge.

Paradoxical Effect of Depression on the Outcomes of Patients Living with Human Immunodeficiency Virus (PLWH) who were Hospitalized due to Acute Myocardial Infarction: A Retrospective Analysis of the National Inpatient Sample Database Between 2010 and 2019

Background: Bariatric surgery (BS) has proved to reduce comorbidity burden among patients with established cardiovascular diseases (CVD). However, its impact on mortality and hospital outcomes remains to be investigated among this population of patients.
Methods: National Inpatient Sample (NIS) database was queried to identify admission cases with CVD during 2019. Mortality rate and hospital outcomes were compared according to the types of CVD and history of BS.
Results: Out of 7,803,805 hospitalizations during 2019, data of 38,354 patients with a history of BS was stratified according to the types of CVD (Table1). History of BS was associated with lower mortality among all CVD subtypes. However, its impact on reducing the length of stay was only statistically significant among established cases of heart failure, atrial fibrillation, peripheral vascular diseases, and aortic dissection/aneurysm. Regardless, previous BS was not associated with lower cost of hospitalization among patients admitted with CVD. Among BS procedures, sleeve gastrectomy played a more beneficial role than gastric bypass among CVD patients.
Conclusion: Bariatric surgery is associated with reduced mortality and length of hospitalization among patients with established CVD with sleeve gastrectomy having a more desirable outcome. However, its impact on acute cases of CVD such as myocardial infarction and cerebrovascular accident remains unclear. 


Bariatric Surgery is Associated with Better Outcomes Among Hospitalized Patients with Established Cardiovascular Diseases in the United States: An Insight from the National Inpatient Sample Data 2019

Background: Sleep disorder (SD) is a common condition in patients suffering cardiovascular conditions. However, its impact on the outcome of certain cardiac events and in the context of co-existing depression has not been studied.
Hypothesis: We wanted to investigate if SD and associated comorbidities affect the outcomes of hospitalized patients with acute myocardial infarction (AMI).
Methods: Using the International Classification of Diseases, tenth revision (ICD-10) codes, we identified admission cases with AMI and SD from the national inpatient sample dataset from 2016 to 2019. Related comorbidities such as depression, drug abuse (DA), and alcohol-related disorders (AD) were also identified using the same approach. Weighted data was analyzed to cross tabulate the mortality rate and frequency of home disposition according to the SD and related comorbidities. A student t-test was also performed to compare the length of hospital stay and total hospital charge between different cohorts of AMI patients.
Results: Data pertinent to 4,483,509 admission cases with AMI was analyzed from 2016 to 2019. Of this, 507,825 patients (11.3%) had a diagnosis of SD, 426,350 patients had depression (9.5%), 919,645 patients (20.5%) had DA, and 174,395 patients (3.9%) had AD. Overall, 362,290 patients (8.1%) died. Mortality rate was significantly higher among AMI patients without SD than in those with SD (8.5% vs. 5.1%, p<0.0001). Among AMI patients with SD, mortality rate and cost of hospitalization was significantly higher in those without depression than in those with depression. On the contrary, AMI patients with SD and depression had a longer LOS and were less likely to be discharged home than AMI patients with SD but without depression. While co-existing DA had a similar effect on these outcome measures as depression, the presence of AD did not affect the mortality rate but reversed other endpoints in AMI patients with SD.
Conclusion: Co-existence of sleep disorder and related comorbidities (depression, drug abuse, and alcohol-related disorder) among patients hospitalized with AMI variably affects the length of stay, hospital charge, destination outcome, and mortality rate. Such paradoxical role play might highlight the variation in other risky behaviors or optimized management among hospitalized AMI patients.

Association of Sleep Disorder with Hospital Outcomes among Hospitalized Patients with Acute Myocardial Infarction in the United States from 2016 to 2019

Introduction
In the thrombolytic era, WHO defined a MI as having 2 out of 3 features of chest pain, ST elevation, and enzyme elevation. These definitions have evolved with the advent of coronary angiography, myocardial imaging, and highly sensitive cardiac enzymes. It is unclear about the proportion of MI patients who have these features in a contemporary setting. We analyzed the MUSC STEMI-Activation database to characterize the presentations of STEMI during 2009-2022.
Method
Medical record of 1113 STEMI activation from 2009-2022 was analyzed using these definitions: 
1) Clinical STEMI- chest pain, diaphoresis, acute dyspnea, and/or cardiac arrest. 
2) EKG STEMI- ST elevation on EKG, new LBBB, reciprocal changes of posterior MI
3) Enzymatic STEMI- rise and fall of hsTroponin (> 10,000 units)
4) Angiographic STEMI-acute culprit vessel identified on angiogram
5) All four features of STEMI-1+2+3+4
Result
There were 1113 consecutive patients identified in the database. The average age was 60 +12.8 years , and they were 70.8% male. Risk factors included hypertension 69.3%, smoking 58.5%, high cholesterol 57.0%, diabetes 30.0%, and chronic kidney disease 10.6%. 
Of the 1113 STEMI activations, 42 (3.8%) patients did not go to the Cath lab (STEMI inactivated). No culprit vessel was detected in 243 patients (22.6%). Of the 1071 patients that went to the Cath lab, angiographic STEMI was detected in 828 patients (77.3%). The culprit vessels were LAD (41.1%), RCA (40.7%), LCX (11.4%), and others (6.8 %). 
Using Angiographic STEMI as the gold standard (n=828), Clinical STEMI was seen in 94.6%, Enzymatic STEMI in 55.8%, and EKG STEMI in 93.0% of this patient population. WHO-defined MI ( 2/3 criteria ) was noted in 776 patients (93.7%). All 4 features of STEMI were noted in only 50.7%.
Conclusion
After STEMI activation, Angiographic STEMI was noted in only 77.3% of cases. WHO defined MI was seen in 93.7% of patients with angiographic STEMI, and all 4 features were seen in 50.7% of patients. Clinical and EKG criteria appeared to be the best predictor of angiographic STEMI. 


Contemporary Patterns of Myocardial Infarction in Patients Presenting with ST- Elevation Myocardial Infarction

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

Next from AMA Research Challenge 2023

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