Comparative Study of Haiti and Miami Cohorts of Sickle Cell Disease (CSHSCD): Methods, Accomplishments, and Implementation

Background: There are significant limitations in Haiti for the diagnosis and management of sickle cell disease (SCD), including the non-availability of universal newborn screening (NBS) and transcranial Doppler (TCD) ultrasound screening, and the lack of diagnostic laboratory resources, oral penicillin and hydroxyurea (HU). Methods: Beginning in September 2019, CSHSCD (R01HL149121), a 5-year NIH-sponsored observational comparative study of children with SCD from Haitian ethnicity in Miami and in Haiti compared to children of African American ethnicity with SCD, was designed to increase access to care in Haiti. The study aims are 1) to compare the incidence of SCD among newborns from Haitian and African American ethnicity in Miami, 2) to establish NBS programs for hemoglobinopathies in Haiti, and 3) to compare cohorts of children in SCD at the study sites. The participating sites are the University of Miami (UM, Miami, Florida), Hôpital Saint Damien (HSD, Tabarre, Haiti), Hôpital de l'Université d'Etat d'Haïti (HUEH, Port-au-Prince, Haiti), Hôpital Universitaire Justinien (HUJ, Cap Haitien, Haiti), and Hôpital Sacré Coeur (HSC, Milot, Haiti). HUJ and HSC use two NBS screening methods (isoelectric focusing and Sickle SCAN rapid test) and HSD and HUEH use isoelectric focusing only. CSHSCD supplies penicillin and HU and trains TCD examiners to implement stroke risk screening. Data are collected in REDCap. Results: During the first 2 years and despite the COVID-19 pandemic, we established NBS sites with a cohesive network of physicians and nurses trained in the care of children with SCD in Haiti. This capacity building will support sustainability of the program. We successfully identified at least 15 new cases of SCD via newborn screening, trained six TCD examiners, and enrolled 130 children with SCD in follow up, providing them with penicillin prophylaxis and hydroxyurea for severe cases according to local protocols . Implementation activities which have helped are close communications between the investigators, monthly Zoom meetings to coordinate efforts with enrollment updates every month, the availability of rapid tests (Sickle SCAN and Gazelle miniature cellulose acetate electrophoresis) for the diagnosis of SCD, especially when there is no laboratory equipment on site. Implementation challenges we have faced are mostly two. The first is the timely completion of DUNS and SAM registration for the two public hospitals, with one site achieving this after 9 months and the other site taking 18 months to complete. The reasons for the delay are the inability for the UM site to direct these efforts, following strict rules, and the Haitian hospital officers' lack of familiarity with website requirements. We were able to achieve these registrations with the assistance of one Haitian study staff who is very acquainted with internet navigation and became familiarized with requirements. Outsourcing materials to Haiti is another major challenge, with either gaps in the delivery of supplies because of multiple steps involved in ordering and shipping or with delays in releasing equipment once it is at the Port-au-Prince customs, resulting in gaps in NBS in one of the sites for 8 weeks. We have minimized these issues by opening a one-year ticket to order materials from the different companies involved. Also, Haiti's lack of infrastructure, available materials and medications, and political instability limit health care delivery. Conclusion: Since its inception, we have achieved major milestones, including capacity building and implementation of NBS, TCD training, and enrollment of children with SCD into the prospective cohorts despite the current COVID-19 pandemic. Material outsourcing challenges have been the major implementation problem we have faced due to systemic factors. We anticipate that these factors will be corrected or minimized as we have learned how to handle them. These problems were expected as part of conducting an international study in a low-resource setting. Acknowledgment: We acknowledge NHLBI for supporting this work. Disclosures Alvarez: Forma Therapeutics: Membership on an entity's Board of Directors or advisory committees; GBT: Membership on an entity's Board of Directors or advisory committees. Romano: Genentech: Research Funding; Vycor: Current holder of individual stocks in a privately-held company; NovaVision: Consultancy.

Evaluation of Anticoagulant Monitoring in Pediatric Patients Receiving Enoxaparin for Treatment of Venous Thrombosis

OBJECTIVES A venous thromboembolism (VTE) is a blood clot that occurs secondary to vessel wall injury often from a central line insertion. Enoxaparin is often considered a first-line treatment in pediatrics for VTE due to its favorable kinetic profile. Enoxaparin monitoring for pediatric patients is accomplished through anti-Xa monitoring in which monitoring practices may vary between institutions. The objective of this study is to evaluate covariates in pediatric patients to determine which variables are most likely to be associated with enoxaparin dose changes as a result of anti-Xa monitoring. METHODS A single center, retrospective chart review was conducted in pediatric patients treated with enoxaparin for VTE over a 10-year period and who were assessed to determine covariates that lead to dose changes based on anti-Xa levels. Secondary outcomes described monitoring patterns at the University of New Mexico Children's Hospital. RESULTS Sixty-eight patients met inclusion criteria in which results showed that patients aged 2 to 5.9 months (p = 0.026), who had critical care status (p = 0.009), and who were of Native American ethnicity (p = 0.016) were likely to have an enoxaparin dose change at least once during their treatment regimen. The mean number of levels drawn were 7.5 per patient over a 6- to 12-week period, and doses were not frequently changed based on a confirmatory lab draw. However, many doses were adjusted based on the week 1 post-therapeutic level. CONCLUSIONS Patients of Native American ethnicity, younger than 6 months, and those admitted to the PICU were likely to have dose changes based on anti-Xa levels.

The Relationship Between Age, Gender, Race, Diabetes and Obesity on Clinical Outcomes in a Large Cohort of Patients Hospitalized for Covid-19 in Metropolitan Detroit

The Severe Acute Respiratory Syndrome Coronavirus-2 infection has resulted in a global pandemic with survival statistics 95–99%, however severe disease has been described. This is a retrospective cohort study of patients > age 18 admitted to Henry Ford Health System in Detroit from March 1 - June 1, 2020 for COVID-19 infection with aims to: 1. Determine the incidence of poor outcomes (mechanical ventilation (MV), ICU admission, death, and venous thromboembolism (VTE)), 2. Describe the clinical characteristics of this group, and 3. Evaluate relationships between demographics, diabetes mellitus (DM), obesity, and inflammatory markers on outcomes. We hypothesized that older age, male gender, African American ethnicity, DM, obesity, and elevated inflammatory markers would predict poor outcomes. 8751 inpatients were included, of whom 682 (7.79%) required MV, 867 (9.91%) were admitted to the ICU, 753 (8.6%) died, and 430 (4.91%) had VTE. 4447 (50.8%) were African American, 4951 (56.6%) female, 5152 (58.9%) > age 50, and 2068 (23.6%) had DM. Of those who had BMI and A1c recorded, 2556 (50.2%) had BMI >30 kg/m2 and 1138 (74.3%) had A1c >5.7%. Analyses controlling for demographics and comorbidities found that age and male gender were significant predictors of MV (OR = 1.031; CI= 1.025–1.037; P < 0.0001, OR =2.023; CI= 1.700–2.407; P<0.0001), ICU admission (OR 1.024; CI= 1.018–1.029; P<0.0001, OR 1.824; CI= 1.561–2.130; P<0.001), death (OR 1.077; CI= 1.069–1.085; P<0.0001, OR 1.823; CI= 1.521–2.185; P<0.0001), and VTE (OR 1.021; CI= 1.014–1.028; P<0.001, OR 1.293; CI= 1.043–1.603; P=0.0193). African American, compared to Caucasian ethnicity, was significantly associated with MV (OR 1.437; CI= 1.131–1.825; P=0.0009) and ICU admission (OR 1.428; CI= 1.150–1.773; P=0.0002), but not VTE. African Americans had significantly lower odds of death relative to Caucasians (OR 0.765; CI=0.604–0.969; P=0.0200). DM predicted MV (OR 1.999; CI= 1.677–2.383; P<0.0001), ICU admission (OR 2.014; CI= 1.717–2.364; P<0.0001), death (OR 1.501; CI= 1.250–1.803; P<0.0001), and VTE (OR 1.468; CI= 1.171–1.840; P=0.0009). Obesity predicted MV (OR 1.540; CI= 1.284–1.847; P<0.0001) and ICU admission (OR 1.395; CI= 1.186–1.642; P<0.0001) but not death or VTE. All inflammatory markers (D-dimer, ferritin, CRP, IL-6 and procalcitonin) were significantly correlated with MV and death. 3 of the 5 markers were also predictive of both ICU admission and VTE. This large retrospective study of a diverse population with a significant proportion of African Americans highlights the importance of taking age, male gender, African American ethnicity, presence of DM and obesity into account when determining risk of poor outcomes. These results contribute to the growing data on disparities in health care which have become more evident during this pandemic and the need to address this when designing public policy.

Study of social disparities in pediatric laparoscopic appendectomy outcomes and cost

Purpose: There is an increasing focus on racial and social disparities in health care. There have been several studies that have documented disparities in outcome between racial groups in the adult literature. Not much is known about disparities in outcomes after surgical procedures in children. The purpose of this study was to investigate the effect of race on complications (outcomes) and costs after laparoscopic appendectomy. Methods: This study is a single-center retrospective chart review of 248 pediatric patients who underwent appendectomies for uncomplicated acute appendicitis from 2015 to 2017. Patients were divided into minority (Africa American or Hispanic) and non-minority groups, and length of stay, preoperative and postoperative factors, and total costs were compared. Results: Of 185 eligible patients, 45.9% (n = 85) were of Hispanic or African American ethnicity and 54.1% (n = 100) were Caucasian. About 11.8% of minority patients had comorbidities and 12% of majority patients had comorbidities (p = 1). Readmission rate for minority group patients was 3.5% (n = 3) and 2% (n = 2) for majority patients (p = 0.7). The average cost of hospital stay for minority patients was $30,900 and for majority patients was $31,111 (p = 0.59). Conclusions: Standardization of care protocols has reduced social/racial disparities in surgical outcomes. In the most common pediatric surgery emergency procedure, laparoscopic appendectomy, there were no differences in outcomes or costs between minority (Hispanic/Africa American) and Caucasian ethnic groups. Level of evidence: Level III Type of study: Clinical Study

High Prevalence of Advanced Liver Fibrosis Assessed by Transient Elastography Among U.S. Adults With Type 2 Diabetes

<b>Objective:</b> Type 2 diabetes mellitus (T2DM) is an important risk factor for the progression of metabolic liver disease to advanced fibrosis. Here, we provide an estimate of the prevalence of steatosis and fibrosis in US adults with T2DM based on transient elastography (TE) and identify factors associated with these conditions. <p><b>Research Design and Methods: </b>This is a cross-sectional study of US adults with T2DM participating in the 2017-2018 cycle of the National Health and Nutrition Examination Survey who were evaluated by TE. Hepatic steatosis and fibrosis were diagnosed by the median value of Controlled Attenuation Parameter (CAP) and Liver Stiffness Measurement (LSM), respectively.</p> <p><b>Results:</b> Among the 825 patients with reliable TE exams, 484 (53.7%) were assessed using the M probe and 341 (46.3%) using the XL probe. Liver steatosis (CAP≥274 dB/m), advanced fibrosis (LSM≥9.7 Kpa) and cirrhosis (LSM≥13.6 Kpa) were present in 73.8% (95% CI 68.5%-78.5%), 15.4% (95% CI 12.2%-19.0%) and 7.7% (95% CI 4.8%-11.9%) of patients, respectively. Mean age of patients with advanced fibrosis and cirrhosis was 63.7 ± 2.2 years and 57.8 ± 1.6 years, respectively. In the multivariable logistic regression model, body mass index (BMI), non-African American ethnicity and alanine aminotransferase levels were independent predictors of steatosis, while BMI, non-African American ethnicity, aspartate aminotransferase and gamma-glutamyltranspeptidase levels were independent predictors of advanced fibrosis.</p> <p><b>Conclusions:</b> Prevalence of both liver steatosis and fibrosis are high in patients with T2DM from the US and obesity is a major risk factor. Our results support the screening of these conditions among diabetic patients.</p>

High Prevalence of Advanced Liver Fibrosis Assessed by Transient Elastography Among U.S. Adults With Type 2 Diabetes

<b>Objective:</b> Type 2 diabetes mellitus (T2DM) is an important risk factor for the progression of metabolic liver disease to advanced fibrosis. Here, we provide an estimate of the prevalence of steatosis and fibrosis in US adults with T2DM based on transient elastography (TE) and identify factors associated with these conditions. <p><b>Research Design and Methods: </b>This is a cross-sectional study of US adults with T2DM participating in the 2017-2018 cycle of the National Health and Nutrition Examination Survey who were evaluated by TE. Hepatic steatosis and fibrosis were diagnosed by the median value of Controlled Attenuation Parameter (CAP) and Liver Stiffness Measurement (LSM), respectively.</p> <p><b>Results:</b> Among the 825 patients with reliable TE exams, 484 (53.7%) were assessed using the M probe and 341 (46.3%) using the XL probe. Liver steatosis (CAP≥274 dB/m), advanced fibrosis (LSM≥9.7 Kpa) and cirrhosis (LSM≥13.6 Kpa) were present in 73.8% (95% CI 68.5%-78.5%), 15.4% (95% CI 12.2%-19.0%) and 7.7% (95% CI 4.8%-11.9%) of patients, respectively. Mean age of patients with advanced fibrosis and cirrhosis was 63.7 ± 2.2 years and 57.8 ± 1.6 years, respectively. In the multivariable logistic regression model, body mass index (BMI), non-African American ethnicity and alanine aminotransferase levels were independent predictors of steatosis, while BMI, non-African American ethnicity, aspartate aminotransferase and gamma-glutamyltranspeptidase levels were independent predictors of advanced fibrosis.</p> <p><b>Conclusions:</b> Prevalence of both liver steatosis and fibrosis are high in patients with T2DM from the US and obesity is a major risk factor. Our results support the screening of these conditions among diabetic patients.</p>

COVID-19 Pandemic Highlights Health Disparities in Latinos in San Diego

Introduction: Minority healthcare disparities are well known in many areas of medicine. Higher mortality has been reported in minorities with different cancer types despite adjusting for income or education. In hematological malignancies the trend persists. Despite favorable prognostic factors upon diagnosis of acute myelogenous leukemia, the mortality risk for Latinos and African Americans is higher by 12% and 7%, respectively. Both incidence and mortality in acute lymphoblastic leukemia are highest in Latinos. In Hodgkin's Lymphoma, Latino and African American adolescents and young adults have a higher risk of death at 35% and 62%, respectively. The COVID-19 pandemic has drawn attention to the immense disparities in healthcare outcomes in minority communities. Disproportionate rates of hospitalization and death related to COVID-19 have been reported across the nation, highlighting the stark consequences of historic racial and economic injustices. With these findings comes a call to action and an urgency to create systemic change to promote health equity. Methods: Patients hospitalized at any Scripps Health hospital in San Diego County from March 1, 2020 to July 30, 2020 with a PCR confirmed diagnosis of COVID-19 and blood type were included in the analysis (n = 316). Demographic, laboratory and clinical data were extracted from the electronic medical record and included age, ethnicity, BMI, sex, medications, co-morbidities, blood type, white blood cell count, lymphocyte count, hemoglobin, platelets, ESR, CRP and D-dimer. Outcomes of interest included length of say (LOS), intensive care unit (ICU) admission, intubation and mortality. Analysis was performed with an a priori predictor of Latin American ethnicity. Linear regression analysis of LOS, logistic regression of other variables and age-adjusted regression was done. Demographic characteristics that were predictive in univariate analysis with p&lt; 0.1 were included in a multiple regression model for each outcome with Latin American ethnicity as a predictor. If the potentially predictive demographic characteristic maintained trends toward significance (p&lt;0.1), the predictor was retained in the model to produce the final regression results for each outcome. Results: Hospitalized COVID patients were predominantly male, obese (BMI 30.6) and average age was 63 years. 69.3% of patients were Hispanic. 65.51% of patients were diabetic, 26.27% had chronic kidney disease and 23.10% had congestive heart failure. Additional patient characteristics are included in Table 1. Median length of hospital stay was 16.5 days, 59% were admitted to the ICU, 37% were intubated, and 27% died. Blood type was not found to be a predictor of outcomes. The odds ratio (OR) of age adjusted LOS for Latinos was 1.01 days (p-value 0.60), 1.06 for ICU admission (p-value 0.80) and 0.82 for death (p-value 0.50). After adjusting for age and other potentially predictive characteristics, Hispanic ethnicity was not predictive of poor outcomes. Conclusion: In this retrospective analysis of patients hospitalized for COVID-19 in San Diego County, there was a strikingly high rate of hospitalizations in Latino patients. While the 2019 United States Census estimates the Latino population in San Diego to be 34.1%, Latinos comprised nearly 70% of patients hospitalized with COVID-19 in the Scripps Health system. Despite the high rate of admissions in Latino patients, Latin American ethnicity was not a predictor of poor outcomes as previously reported in other populations. The underlying etiology of the high rates of COVID-19 hospital admission in Latinos is likely multifactorial due to overcrowding, lack of access to healthcare and higher prevalence of chronic illness as demonstrated by our cohort's increased incidence of co-morbid conditions. Disclosures No relevant conflicts of interest to declare.